CHARACTERIZATION OF ETHOSUXIMIDE REDUCTION OF LOW-THRESHOLD CALCIUM CURRENT IN THALAMIC NEURONS
CHARACTERIZATION OF ETHOSUXIMIDE REDUCTION OF LOW-THRESHOLD CALCIUM CURRENT IN THALAMIC NEURONS
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DOI：
10.1002/ana.410250610
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发表时间：
1989-06-01
影响因子：
11.2
通讯作者：
PRINCE, DA
中科院分区：
文献类型：
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作者：
COULTER, DA;HUGUENARD, JR;PRINCE, DA
在急性分离的大鼠和豚鼠腹侧基底核复合体神经元上，用电压钳技术分析了乙琥胺降低丘脑低阈值钙电流（LTCC）的机制。乙琥胺诱导的LTCC的减少是电压依赖性的：在更超极化的电位下不明显，并且不影响电流激活的时间过程。乙琥胺降低LTCC而不改变稳态失活的电压依赖性或失活恢复的时间过程。二甲双酮通过类似的机制降低LTCC，而丙戊酸对LTCC没有影响。我们的结论是，乙琥胺减少丘脑神经元中的LTCC与可用的LTCC通道或在单个LTCC通道电导的数量减少是一致的，这可能表明这种药物的直接通道阻断作用。鉴于LTCC在丘脑振荡行为中的重要性，乙琥胺降低该电流将是一种与该药物在典型失神发作中的已知抗惊厥作用相容的作用机制。
The mechanism by which ethosuximide reduces thalamic low-threshold calcium current (LTCC) was analyzed using voltage-clamp technique in acutely isolated ventrobasal complex neurons from rats and guinea pigs. The ethosuximide-induced reduction of LTCC was voltage dependent: it was not pronounced at more hyperpolarized potentials and did not affect the time course of activation of the current. Ethosuximide reduced LTCC without altering the voltage dependence of steady-state inactivation or the time course of recovery from inactivation. Dimethadione reduced LTCC by a similar mechanism, while valproic acid had no effect on LTCC. We conclude that ethosuximide reduction of LTCC in thalamic neurons is consistent with a reduction in the number of available LTCC channels or in the single LTCC channel conductance, perhaps indicating a direct channel-blocking action of this drug. Given the importance of LTCC in thalamic oscillatory behavior, a reduction in this current by ethosuximide would be a mechanism of action compatible with the known anticonvulsant effects of this drug in typical absence seizures.