Aicardi G, Schwartzkroin P A
Department of Neurological Surgery, University of Washington, Seattle 98195.
Exp Brain Res. 1990;81(2):288-96. doi: 10.1007/BF00228118.
We studied the effects of the organic calcium channel blocker, verapamil, on spontaneous and bicuculine-induced epileptiform burst discharges in CA3 pyramidal cells of hippocampal slices. A transient increase of burst discharge rate was observed in most cells within 30 min after the addition of verapamil (100 microM) to the perfusing medium. Prolonged verapamil perfusions gradually reduced the rate and duration of burst discharges, then abolished them in all tested slices (over periods of 50-150 min) without blocking synaptic transmission. Responses to intracellular injections of current pulses were also gradually affected by verapamil: Action potential amplitude was decreased, action potential duration increased, frequency adaptation increased, amplitude of the fast hyperpolarization following a single action potential decreased, and amplitude and duration of the slow afterhyperpolarization markedly reduced. The amplitude of calcium spikes elicited in slices perfused with tetrodotoxin-containing medium was not affected by verapamil, but the mean velocity of depolarization near the peak of the calcium spike was decreased. Membrane resting potential and input resistance were not affected by verapamil. These results confirm that verapamil is able to suppress epileptiform activity, but suggest that this effect is rather non-specific, due to inhibition of both postsynaptic sodium and calcium conductances.
我们研究了有机钙通道阻滞剂维拉帕米对海马切片CA3锥体细胞自发性和荷包牡丹碱诱导的癫痫样爆发放电的影响。在向灌注培养基中添加维拉帕米（100 microM）后30分钟内，大多数细胞中观察到爆发放电率短暂增加。长时间灌注维拉帕米会逐渐降低爆发放电的速率和持续时间，然后在所有测试切片中（50 - 150分钟内）消除爆发放电，且不阻断突触传递。维拉帕米也会逐渐影响对细胞内注射电流脉冲的反应：动作电位幅度降低，动作电位持续时间增加，频率适应性增加，单个动作电位后的快速超极化幅度降低，慢后超极化的幅度和持续时间明显减少。在用含河豚毒素的培养基灌注的切片中诱发的钙峰幅度不受维拉帕米影响，但钙峰峰值附近的去极化平均速度降低。膜静息电位和输入电阻不受维拉帕米影响。这些结果证实维拉帕米能够抑制癫痫样活动，但表明这种作用相当非特异性，这是由于对突触后钠和钙电导的抑制。
