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首页> 外文期刊>Journal of Neurophysiology >Functional characterization of the effect of nimodipine on the calcium current in rat cerebellar granule cells.
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Functional characterization of the effect of nimodipine on the calcium current in rat cerebellar granule cells.

机译：尼莫地平对大鼠小脑颗粒细胞钙电流影响的功能表征。

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1. We investigated the effect of nimodipine on the calcium current in dissociated cerebellar granule cells from 8-day-old rats. We measured the whole cell current and the depolarization-induced internal calcium elevation in Fura2-loaded cells exposed to high-potassium solutions. 2. Nimodipine maximally depressed the peak calcium current from holding potential (Vh) = -80 mV by 25% and the inactivation resistant residual current from Vh = -50 mV by 44%. The nimodipine-sensitive current had the same amplitude under both conditions and the half-maximal inhibition concentration (IC50) was close to 50 nM. 3. In contrast to other components of the calcium current, the nimodipine-sensitive current did not inactivate significantly during 1-s depolarization and it was weakly sensitive to the holding potential and to depolarizing conditioning prepulses. The effect of nimodipine was higher on the current elicited by small depolarizations and the current at -30 mV was depressed by < or = 70%. Depolarizing prepulsesenhanced the effect of 1 nM (but not that of 1 microM) nimodipine. 4. In Fura2-loaded cells, nimodipine strongly antagonized the internal calcium rise due to superfusion with 15-75 mM potassium. The effect was significantly more potent on the internal calcium rise determined by lower depolarizations, with 80% inhibition of the peak response to 25 mM KCl. The dose dependence of this depression was best approximated by a two-site curve with IC50(1) = 0.27 nM and IC50(2) = 65 nM. The time course of recovery was dependent on the duration of treatment, suggesting a close interaction between nimodipine and the lipid membrane. 5. The effect of 1 microM nimodipine was not influenced by predepolarizations determined by treatments with calcium-free elevated potassium solutions, but when doses as low as 1 nM were applied the fast decay of the calcium level suggested a voltage dependence of the effect. Nimodipine also depressed < or = 90% of the plateau phase of the depolarization-induced internal calcium rise at different depolarizations. 6. Incubation in omega-conotoxin, fraction GVIA (5 microM) did not cause any significant decrease in the calcium response, whereas omega-agatoxin, fraction IVA (0.5 microM) depressed the calcium peak by 40-60% and its effect was additive with that of nimodipine. 7. We conclude that the nimodipine-sensitive current is a persistent, inactivation-resistant current that activates at a membrane potential lower than the other components and is likely to be responsible for the elevation of calcium determined by nonovershooting, prolonged depolarizations in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
机译：1.我们研究了尼莫地平对8日龄大鼠离解的小脑颗粒细胞中钙电流的影响。我们测量了暴露于高钾溶液中的Fura2负载细胞的全细胞电流和去极化诱导的内部钙离子升高。 2.尼莫地平将最大钙电流从保持电位（Vh）= -80 mV降低25％，将抗灭活残余电流从Vh = -50 mV降低44％。尼莫地平敏感电流在两个条件下均具有相同的幅度，半最大抑制浓度（IC50）接近50 nM。 3.与钙电流的其他成分相反，对尼莫地平敏感的电流在1-s去极化过程中并未显着失活，并且对保持电位和对调节预脉冲的去极化敏感。尼莫地平对小的去极化引起的电流的影响更高，并且在-30 mV的电流被抑制了<或= 70％。去极化前脉冲增强了1 nM（但不是1 microM）尼莫地平的作用。 4.在装有Fura2的细胞中，尼莫地平强烈拮抗由于与15-75 mM钾的过度灌注而引起的内部钙升高。通过较低的去极化确定的内部钙升高效果更显着，对25 mM KCl的峰响应抑制80％。这种抑郁症的剂量依赖性最好通过两点曲线来近似表示，IC50（1）= 0.27 nM，IC50（2）= 65 nM。恢复的时间过程取决于治疗的持续时间，表明尼莫地平和脂质膜之间存在紧密的相互作用。 5. 1 microM尼莫地平的作用不受无钙高钾溶液处理所确定的去极化作用的影响，但是当剂量低至1 nM时，钙水平的快速衰减表明该作用的电压依赖性。尼莫地平还抑制了在不同去极化时去极化诱导的内部钙上升的平台期的≤90％。 6.在ω-芋螺毒素（GVIA级分（5 microM））中孵育不会引起钙反应的任何显着降低，而ω-aga毒素（IVA级分（0.5 microM））使钙峰值降低了40-60％，其作用是累加的与尼莫地平一样。 7.我们得出的结论是，对尼莫地平敏感的电流是一种持续的，抗失活的电流，该电流在比其他成分低的膜电位下激活，并且可能是由这些细胞中非过度调节，长时间去极化确定的钙升高的原因。 （摘要以400字截断）

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