Targeting BK (big potassium) channels in epilepsy.
Targeting BK (big potassium) channels in epilepsy.
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DOI：
10.1517/14728222.2011.620607
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发表时间：
2011-11
影响因子：
5.8
通讯作者：
N'Gouemo P
中科院分区：
文献类型：
--
作者：
N'Gouemo P
Epilepsies are disorders of neuronal excitability characterized by spontaneous and recurrent seizures. Ion channels are critical for regulating neuronal excitability and, therefore, can contribute significantly to epilepsy pathophysiology. In particular, large conductance, Ca2+-activated K+ (BKCa) channels play an important role in seizure etiology. These channels are activated by both membrane depolarization and increased intracellular Ca2+. This unique coupling of Ca2+ signaling to membrane depolarization is important in controlling neuronal hyperexcitability, as outward K+ current through BKCa channels hyperpolarizes neurons. This review focuses on BKCa channel structure-function and discusses the role of these channels in epilepsy pathophysiology. Loss-of-function BKCa channels contribute neuronal hyperexcitability that can lead to temporal lobe epilepsy, tonic-clonic seizures and alcohol withdrawal seizures. Similarly, BKCa channel blockade can trigger seizures and status epilepticus. Paradoxically, some mutations in BKCa channel subunit can give rise to the channel gain-of-function that leads to development of idiopathic epilepsy (primarily absence epilepsy). Seizures themselves also enhance BKCa channel currents associated with neuronal hyperexcitability, and blocking BKCa channels suppresses generalized tonic-clonic seizures. Thus, both loss-of-function and gain-of-function BKCa channels might serve as molecular targets for drugs to suppress certain seizure phenotypes including temporal lobe seizures and absence seizures, respectively.
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影响因子：
2.9
作者：
Ermolinsky BS;Skinner F;Garcia I;Arshadmansab MF;Otalora LF;Zarei MM;Garrido-Sanabria ER
通讯作者：
Garrido-Sanabria ER
影响因子：
16.8
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Hoshi, Toshinori
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Brenner, R;Jegla, TJ;Aldrich, RW
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Aldrich, RW
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Cavalleri, Gianpiero L.;Weale, Michael E.;Goldstein, David B.
通讯作者：
Goldstein, David B.
影响因子：
2.9
作者：
GUILLEMARE, E;HONORE, E;LAZDUNSKI, M
通讯作者：
LAZDUNSKI, M