Ignet

Gene Information

Gene symbol: KCNA3

Gene name: potassium voltage-gated channel, shaker-related subfamily, member 3

HGNC ID: 6221

Synonyms: Kv1.3, MK3, HLK3, HPCN3

Related Genes

#	Gene Symbol	Number of hits
1	ACCN2	1 hits
2	ATP1B1	1 hits
3	BSND	1 hits
4	CACNA1C	1 hits
5	CACNA1G	1 hits
6	CACNA1H	1 hits
7	CACNA2D1	1 hits
8	CACNB1	1 hits
9	CACNB2	1 hits
10	CCDC91	1 hits
11	CD4	1 hits
12	CFTR	1 hits
13	CLCN2	1 hits
14	GJA4	1 hits
15	GRIK2	1 hits
16	HCN2	1 hits
17	INS	1 hits
18	INSR	1 hits
19	KCNA1	1 hits
20	KCNA2	1 hits
21	KCNA4	1 hits
22	KCNA5	1 hits
23	KCNAB1	1 hits
24	KCNB1	1 hits
25	KCND1	1 hits
26	KCND3	1 hits
27	KCNE1	1 hits
28	KCNG2	1 hits
29	KCNH2	1 hits
30	KCNIP2	1 hits
31	KCNJ1	1 hits
32	KCNJ2	1 hits
33	KCNJ3	1 hits
34	KCNK3	1 hits
35	KCNN2	1 hits
36	KCNN4	1 hits
37	KCNQ1	1 hits
38	KCNQ4	1 hits
39	PDAP1	1 hits
40	RP9	1 hits
41	SCN1B	1 hits
42	SCN5A	1 hits
43	SGK1	1 hits
44	SHPK	1 hits
45	SLC2A4	1 hits
46	TPM2	1 hits

Related Sentences

#	PMID	Sentence
1	14981264	The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.
2	14981264	Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes.
3	14981264	Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels.
4	14981264	This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity.
5	14981264	Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo.
6	14981264	Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice.
7	14981264	Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane.
8	14981264	It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue.
9	14981264	We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane.
10	14981264	The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.
11	14981264	Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes.
12	14981264	Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels.
13	14981264	This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity.
14	14981264	Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo.
15	14981264	Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice.
16	14981264	Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane.
17	14981264	It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue.
18	14981264	We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane.
19	14981264	The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.
20	14981264	Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes.
21	14981264	Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels.
22	14981264	This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity.
23	14981264	Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo.
24	14981264	Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice.
25	14981264	Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane.
26	14981264	It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue.
27	14981264	We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane.
28	14981264	The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.
29	14981264	Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes.
30	14981264	Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels.
31	14981264	This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity.
32	14981264	Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo.
33	14981264	Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice.
34	14981264	Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane.
35	14981264	It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue.
36	14981264	We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane.
37	14981264	The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.
38	14981264	Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes.
39	14981264	Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels.
40	14981264	This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity.
41	14981264	Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo.
42	14981264	Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice.
43	14981264	Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane.
44	14981264	It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue.
45	14981264	We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane.
46	14981264	The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.
47	14981264	Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes.
48	14981264	Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels.
49	14981264	This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity.
50	14981264	Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo.
51	14981264	Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice.
52	14981264	Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane.
53	14981264	It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue.
54	14981264	We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane.
55	14981264	The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.
56	14981264	Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes.
57	14981264	Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels.
58	14981264	This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity.
59	14981264	Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo.
60	14981264	Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice.
61	14981264	Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane.
62	14981264	It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue.
63	14981264	We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane.
64	15948674	Kv1.3 potassium channel blockade as an approach to insulin resistance.
65	15948674	Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism.
66	15948674	Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane.
67	15948674	In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.
68	15948674	Kv1.3 potassium channel blockade as an approach to insulin resistance.
69	15948674	Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism.
70	15948674	Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane.
71	15948674	In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.
72	15948674	Kv1.3 potassium channel blockade as an approach to insulin resistance.
73	15948674	Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism.
74	15948674	Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane.
75	15948674	In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.
76	15948674	Kv1.3 potassium channel blockade as an approach to insulin resistance.
77	15948674	Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism.
78	15948674	Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane.
79	15948674	In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.
80	16176826	We have previously demonstrated in a heterologous system that insulin modulates the voltage-dependent potassium channel, Kv1.3, through tyrosine phosphorylation of three key residues in the amino and carboxyl terminus of the channel protein.
81	16317062	A new variant in the human Kv1.3 gene is associated with low insulin sensitivity and impaired glucose tolerance.
82	16787250	In this review the basic properties and physiological roles of the voltage-gated Kv1.3 and the Ca2+-activated IKCa1 potassium channels are discussed along with an overview of compounds inhibiting these channels and approaches aiming at producing more efficient modulators of immune functions for the treatment of diseases like sclerosis multiplex and type I diabetes.
83	17088564	Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression.
84	17088564	In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4.
85	17088564	Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells.
86	17088564	Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression.
87	17088564	In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4.
88	17088564	Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells.
89	17088564	Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression.
90	17088564	In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4.
91	17088564	Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells.
92	17659485	After initially being pursued for general immunosuppression, the voltage-gated potassium channel Kv1.3 has more recently emerged as an attractive pharmacological target for the selective suppression of CCR7- effector memory T-cells in T-cell mediated autoimmune diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and psoriasis.
93	17984097	It blocked Kv1.3 with K(d) 36 nm (2,800-fold lower affinity than ShK), was 2-fold selective for Kv1.3 over Kv1.1, and was inactive against other K(+) channels tested.
94	19458242	The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues.
95	19458242	We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting.
96	19458242	The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues.
97	19458242	We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting.
98	20954790	This article evaluates a patent application from Solvay Pharmaceuticals, which claims spiro azepane-oxazolidinones as novel blockers of the voltage-gated potassium channel Kv1.3 for the treatment of diabetes, psoriasis, obesity, transplant rejection and T-cell mediated autoimmune diseases such as rheumatoid arthritis and MS.
99	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
100	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
101	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
102	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
103	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
104	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
105	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
106	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
107	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
108	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
109	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
110	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
111	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
112	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
113	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
114	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
115	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
116	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
117	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
118	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
119	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
120	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
121	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
122	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
123	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
124	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
125	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
126	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
127	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
128	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
129	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
130	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
131	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
132	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
133	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
134	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
135	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
136	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
137	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
138	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
139	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
140	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
141	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
142	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
143	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
144	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
145	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
146	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
147	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
148	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
149	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
150	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
151	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
152	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
153	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
154	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
155	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
156	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
157	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
158	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
159	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
160	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
161	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
162	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
163	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
164	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
165	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
166	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
167	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
168	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
169	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
170	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
171	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
172	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
173	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
174	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
175	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
176	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
177	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
178	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
179	21586699	Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues.
180	21586699	Genetic ablation of the voltage-gated potassium channel Kv1.3 improves insulin sensitivity and increases metabolic rate in mice.
181	21586699	Inhibition of Kv1.3 in mouse adipose and skeletal muscle is reported to increase glucose uptake through increased GLUT4 translocation.
182	21586699	Since Kv1.3 represents a novel target for the treatment of diabetes, the present study investigated whether Kv1.3 is functionally expressed in human adipose and skeletal muscle and whether specific pharmacological inhibition of the channel is capable of modulating insulin sensitivity in diabetic mouse models.
183	21586699	Voltage-gated K(+) channel currents in human skeletal muscle cells (SkMC) were insensitive to block by the specific Kv1.3 blockers 5-(4-phenoxybutoxy)psoralen (PAP-1) and margatoxin (MgTX).
184	21586699	To investigate the effect of specific Kv1.3 inhibition on insulin sensitivity in vivo, PAP-1 was administered to hyperglycemic mice either acutely or for 5 days prior to an insulin tolerance test.
185	21586699	No effect on insulin sensitivity was observed at free plasma PAP-1 concentrations that are specific for inhibition of Kv1.3.
186	21586699	Insulin sensitivity was increased only when plasma concentrations of PAP-1 were sufficient to inhibit other Kv1 channels.
187	21586699	Surprisingly, acute inhibition of Kv1.3 in the brain was found to decrease insulin sensitivity in ob/ob mice.
188	21586699	Overall, these findings are not supportive of a role for Kv1.3 in the modulation of peripheral insulin sensitivity.
189	21966386	We here uncovered that the olfactory bulb (OB) subserves as an internal sensor of metabolism via insulin-induced modulation of the potassium channel Kv1.3.
190	21966386	Using an adult slice preparation of the olfactory bulb, we found that evoked neural activity in Kv1.3-expressing mitral cells is enhanced following acute insulin application.
191	21966386	Insulin mediated changes in mitral cell excitability are predominantly due to the modulation of Kv1.3 channels as evidenced by the lack of effect in slices from Kv1.3-null mice.
192	21966386	Moreover, a selective Kv1.3 peptide blocker (ShK186) inhibits more than 80% of the outward current in parallel voltage-clamp studies, whereby insulin significantly decreases the peak current magnitude without altering the kinetics of inactivation or deactivation.
193	21966386	We here uncovered that the olfactory bulb (OB) subserves as an internal sensor of metabolism via insulin-induced modulation of the potassium channel Kv1.3.
194	21966386	Using an adult slice preparation of the olfactory bulb, we found that evoked neural activity in Kv1.3-expressing mitral cells is enhanced following acute insulin application.
195	21966386	Insulin mediated changes in mitral cell excitability are predominantly due to the modulation of Kv1.3 channels as evidenced by the lack of effect in slices from Kv1.3-null mice.
196	21966386	Moreover, a selective Kv1.3 peptide blocker (ShK186) inhibits more than 80% of the outward current in parallel voltage-clamp studies, whereby insulin significantly decreases the peak current magnitude without altering the kinetics of inactivation or deactivation.
197	21966386	We here uncovered that the olfactory bulb (OB) subserves as an internal sensor of metabolism via insulin-induced modulation of the potassium channel Kv1.3.
198	21966386	Using an adult slice preparation of the olfactory bulb, we found that evoked neural activity in Kv1.3-expressing mitral cells is enhanced following acute insulin application.
199	21966386	Insulin mediated changes in mitral cell excitability are predominantly due to the modulation of Kv1.3 channels as evidenced by the lack of effect in slices from Kv1.3-null mice.
200	21966386	Moreover, a selective Kv1.3 peptide blocker (ShK186) inhibits more than 80% of the outward current in parallel voltage-clamp studies, whereby insulin significantly decreases the peak current magnitude without altering the kinetics of inactivation or deactivation.
201	21966386	We here uncovered that the olfactory bulb (OB) subserves as an internal sensor of metabolism via insulin-induced modulation of the potassium channel Kv1.3.
202	21966386	Using an adult slice preparation of the olfactory bulb, we found that evoked neural activity in Kv1.3-expressing mitral cells is enhanced following acute insulin application.
203	21966386	Insulin mediated changes in mitral cell excitability are predominantly due to the modulation of Kv1.3 channels as evidenced by the lack of effect in slices from Kv1.3-null mice.
204	21966386	Moreover, a selective Kv1.3 peptide blocker (ShK186) inhibits more than 80% of the outward current in parallel voltage-clamp studies, whereby insulin significantly decreases the peak current magnitude without altering the kinetics of inactivation or deactivation.
205	22241939	The Lymphocyte Potassium Channels Kv1.3 and KCa3.1 as Targets for Immunosuppression.
206	22241939	The voltage-gated Kv1.3 and the calcium-activated KCa3.1 potassium channel modulate many calcium-dependent cellular processes in immune cells, including T-cell activation and proliferation, and have therefore been proposed as novel therapeutic targets for immunomodulation.
207	22241939	Results from animal studies have been supportive of the therapeutic potential of both Kv1.3 and KCa3.1 blockers and have also not shown any toxicities associated with pharmacological Kv1.3 and KCa3.1 blockade.
208	22241939	The Lymphocyte Potassium Channels Kv1.3 and KCa3.1 as Targets for Immunosuppression.
209	22241939	The voltage-gated Kv1.3 and the calcium-activated KCa3.1 potassium channel modulate many calcium-dependent cellular processes in immune cells, including T-cell activation and proliferation, and have therefore been proposed as novel therapeutic targets for immunomodulation.
210	22241939	Results from animal studies have been supportive of the therapeutic potential of both Kv1.3 and KCa3.1 blockers and have also not shown any toxicities associated with pharmacological Kv1.3 and KCa3.1 blockade.
211	22241939	The Lymphocyte Potassium Channels Kv1.3 and KCa3.1 as Targets for Immunosuppression.
212	22241939	The voltage-gated Kv1.3 and the calcium-activated KCa3.1 potassium channel modulate many calcium-dependent cellular processes in immune cells, including T-cell activation and proliferation, and have therefore been proposed as novel therapeutic targets for immunomodulation.
213	22241939	Results from animal studies have been supportive of the therapeutic potential of both Kv1.3 and KCa3.1 blockers and have also not shown any toxicities associated with pharmacological Kv1.3 and KCa3.1 blockade.
214	22581745	Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle.
215	22581745	The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle.
216	22581745	The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0.03 versus 0.80 ± 0.11; Kcna4, 0.79 ± 0.25 versus 1.90 ± 0.26; and Kcnj2, 0.52 ± 0.07 versus 0.78 ± 0.08) in GK ventricle compared with control ventricle.
217	22659540	Expression and isotopic labelling of the potassium channel blocker ShK toxin as a thioredoxin fusion protein in bacteria.
218	22659540	The polypeptide toxin ShK is a potent blocker of Kv1.3 potassium channels, which play a crucial role in the activation of human effector memory T-cells (T(EM)).
219	22659540	ShK was expressed as a thioredoxin fusion protein in Escherichia coli BL21 (DE3) cells and purified initially by Ni²⁺ iminodiacetic acid affinity chromatography.
220	22659540	Recombinant ShK blocked Kv1.3 channels with a K(d) of 25 pM and inhibited the proliferation of human and rat T lymphocytes with a preference for T(EM) cells, with similar potency to synthetic ShK in all assays.
221	22659540	This expression system also enables the efficient production of ¹⁵N-labelled ShK for NMR studies of peptide dynamics and of the interaction of ShK with Kv1.3 channels.
222	22659540	Expression and isotopic labelling of the potassium channel blocker ShK toxin as a thioredoxin fusion protein in bacteria.
223	22659540	The polypeptide toxin ShK is a potent blocker of Kv1.3 potassium channels, which play a crucial role in the activation of human effector memory T-cells (T(EM)).
224	22659540	ShK was expressed as a thioredoxin fusion protein in Escherichia coli BL21 (DE3) cells and purified initially by Ni²⁺ iminodiacetic acid affinity chromatography.
225	22659540	Recombinant ShK blocked Kv1.3 channels with a K(d) of 25 pM and inhibited the proliferation of human and rat T lymphocytes with a preference for T(EM) cells, with similar potency to synthetic ShK in all assays.
226	22659540	This expression system also enables the efficient production of ¹⁵N-labelled ShK for NMR studies of peptide dynamics and of the interaction of ShK with Kv1.3 channels.
227	22659540	Expression and isotopic labelling of the potassium channel blocker ShK toxin as a thioredoxin fusion protein in bacteria.
228	22659540	The polypeptide toxin ShK is a potent blocker of Kv1.3 potassium channels, which play a crucial role in the activation of human effector memory T-cells (T(EM)).
229	22659540	ShK was expressed as a thioredoxin fusion protein in Escherichia coli BL21 (DE3) cells and purified initially by Ni²⁺ iminodiacetic acid affinity chromatography.
230	22659540	Recombinant ShK blocked Kv1.3 channels with a K(d) of 25 pM and inhibited the proliferation of human and rat T lymphocytes with a preference for T(EM) cells, with similar potency to synthetic ShK in all assays.
231	22659540	This expression system also enables the efficient production of ¹⁵N-labelled ShK for NMR studies of peptide dynamics and of the interaction of ShK with Kv1.3 channels.
232	23012321	SGK1 is activated by insulin and growth factors through PI3K and 3-phosphoinositide-dependent kinase PDK1.
233	23012321	SGK1 activates a wide variety of ion channels (e.g., ENaC, SCN5A, TRPV4-6, ROMK, Kv1.3, Kv1.5, Kv4.3, KCNE1/KCNQ1, KCNQ4, ASIC1, GluR6, ClCKa/barttin, ClC2, CFTR, and Orai/STIM), which participate in the regulation of transport, hormone release, neuroexcitability, inflammation, cell proliferation, and apoptosis.
234	23620341	Expression of mRNA encoding Tpm2, Gja4, Atp1b1, Cacna1g, Cacnb2, Hcn2, Kcna3 and Kcne1 were up-regulated and Gja1, Kcnj2 and Kcnk3 were down-regulated in hearts of sedentary GK rats compared to sedentary controls.
235	23620341	Gja1, Cav3 and Kcnk3 were up-regulated and Hcn2 was down-regulated in hearts of exercise trained GK compared to sedentary GK controls.
236	23729813	Selective Kv1.3 channel blocker as therapeutic for obesity and insulin resistance.
237	23729813	ShK-186 reduced weight gain, adiposity, and fatty liver; decreased blood levels of cholesterol, sugar, HbA1c, insulin, and leptin; and enhanced peripheral insulin sensitivity.
238	23729813	Our results highlight the potential use of Kv1.3 blockers for the treatment of obesity and insulin resistance.
239	23729813	Selective Kv1.3 channel blocker as therapeutic for obesity and insulin resistance.
240	23729813	ShK-186 reduced weight gain, adiposity, and fatty liver; decreased blood levels of cholesterol, sugar, HbA1c, insulin, and leptin; and enhanced peripheral insulin sensitivity.
241	23729813	Our results highlight the potential use of Kv1.3 blockers for the treatment of obesity and insulin resistance.
242	16099841	Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases.
243	16099841	Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5.
244	16099841	By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern.
245	16099841	The most potent and "drug-like" compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel.
246	16099841	PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels.
247	16099841	PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations.
248	16099841	PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.
249	16099841	Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases.
250	16099841	Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5.
251	16099841	By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern.
252	16099841	The most potent and "drug-like" compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel.
253	16099841	PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels.
254	16099841	PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations.
255	16099841	PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.
256	16099841	Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases.
257	16099841	Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5.
258	16099841	By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern.
259	16099841	The most potent and "drug-like" compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel.
260	16099841	PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels.
261	16099841	PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations.
262	16099841	PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.
263	16099841	Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases.
264	16099841	Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5.
265	16099841	By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern.
266	16099841	The most potent and "drug-like" compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel.
267	16099841	PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels.
268	16099841	PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations.
269	16099841	PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.
270	16099841	Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases.
271	16099841	Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5.
272	16099841	By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern.
273	16099841	The most potent and "drug-like" compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel.
274	16099841	PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels.
275	16099841	PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations.
276	16099841	PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.