Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.
BACKGROUND: The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. OBJECTIVE: To identify mechanisms of temperature dependency in this channelopathy. METHODS: Using the amp...
| Main Authors: | , , , , , , , |
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| Format: | Conference item |
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2003
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| _version_ | 1797101696491454464 |
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| author | Sugiura, Y Makita, N Li, L Noble, P Kimura, J Kumagai, Y Soeda, T Yamamoto, T |
| author_facet | Sugiura, Y Makita, N Li, L Noble, P Kimura, J Kumagai, Y Soeda, T Yamamoto, T |
| author_sort | Sugiura, Y |
| collection | OXFORD |
| description | BACKGROUND: The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. OBJECTIVE: To identify mechanisms of temperature dependency in this channelopathy. METHODS: Using the amphotericin B perforated patch clamp method, sodium currents were recorded at 22 and 32 degrees C from the wild-type (WT) and P1158S mutant SCN4A expressed in tsA201 cells. Computer simulation was performed, incorporating the gating parameters of the P1158S mutant SCN4A. RESULTS: P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold and myotonia at a normal potassium concentration. CONCLUSIONS: Both paralysis and myotonia are attributable to the biophysical properties of the SCN4A mutation associated with hypoKPP. This is the first report of an SCN4A mutation that exhibits temperature-dependent shifts of voltage dependence in sodium channel gating. |
| first_indexed | 2024-03-07T05:55:29Z |
| format | Conference item |
| id | oxford-uuid:ea5a5a87-2ce0-4bde-bc30-9441b3ab56fb |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:55:29Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:ea5a5a87-2ce0-4bde-bc30-9441b3ab56fb2022-03-27T11:01:31ZCold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.Conference itemhttp://purl.org/coar/resource_type/c_5794uuid:ea5a5a87-2ce0-4bde-bc30-9441b3ab56fbSymplectic Elements at Oxford2003Sugiura, YMakita, NLi, LNoble, PKimura, JKumagai, YSoeda, TYamamoto, TBACKGROUND: The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. OBJECTIVE: To identify mechanisms of temperature dependency in this channelopathy. METHODS: Using the amphotericin B perforated patch clamp method, sodium currents were recorded at 22 and 32 degrees C from the wild-type (WT) and P1158S mutant SCN4A expressed in tsA201 cells. Computer simulation was performed, incorporating the gating parameters of the P1158S mutant SCN4A. RESULTS: P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold and myotonia at a normal potassium concentration. CONCLUSIONS: Both paralysis and myotonia are attributable to the biophysical properties of the SCN4A mutation associated with hypoKPP. This is the first report of an SCN4A mutation that exhibits temperature-dependent shifts of voltage dependence in sodium channel gating. |
| spellingShingle | Sugiura, Y Makita, N Li, L Noble, P Kimura, J Kumagai, Y Soeda, T Yamamoto, T Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. |
| title | Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. |
| title_full | Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. |
| title_fullStr | Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. |
| title_full_unstemmed | Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. |
| title_short | Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. |
| title_sort | cold induces shifts of voltage dependence in mutant scn4a causing hypokalemic periodic paralysis |
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