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ryanodine、乙二醇双乙醚二胺四乙酸(EGTA)和低钠对大鼠和豚鼠心室肌细胞动作电位的影响:平台期两种内向电流的证据

The effects of ryanodine, EGTA and low-sodium on action potentials in rat and guinea-pig ventricular myocytes: evidence for two inward currents during the plateau.

作者信息

Mitchell M R, Powell T, Terrar D A, Twist V W

出版信息

Br J Pharmacol. 1984 Mar;81(3):543-50. doi: 10.1111/j.1476-5381.1984.tb10107.x.

Abstract

Action potentials were recorded from single cells isolated from rat and guinea-pig ventricular muscle. In rat cells the repolarization showed two distinct phases, referred to as the early and late phases. In guinea-pig cells there was a maintained plateau. Reducing external sodium by replacement with lithium or choline suppressed the late phase of the action potential in rat cells, and shortened the plateau of the action potential in guinea-pig cells. Intracellular EGTA abolished contraction while suppressing the late phase of the action potential in rat cells, and shortening the plateau in guinea-pig cells. Ryanodine (1 microM), which is thought to inhibit the release of calcium from internal stores, suppressed contraction and the late phase of the action potential in rat cells. In guinea-pig cells, there was no substantial effect of ryanodine (1 microM) on either contraction or the time course of the action potential. The late phase of the action potential in rat cells was suppressed by increasing the external potassium concentration to 12 mM, and enhanced by reducing external potassium to 1.2 mM. It is concluded that an inward current activated by internal calcium contributes to the late phase of the action potential in rat cells, and to the plateau in guinea-pig cells. Two possibilities are a current arising from electrogenic sodium-calcium exchange, and a current through ion channels activated by calcium. The effects of reducing external sodium would be consistent with either mechanism. The contribution of such an inward current would be expected to be modified by outward currents through a rectifying potassium conductance which varies with external potassium concentration. In the rat, but not the guinea-pig, the rise in internal calcium which activates the inward current seems to be largely dependent on ryanodine-sensitive release of calcium from internal stores.

摘要

从大鼠和豚鼠心室肌分离出的单细胞记录动作电位。在大鼠细胞中,复极化呈现两个不同阶段,即早期和晚期。在豚鼠细胞中,存在一个持续的平台期。用锂或胆碱替代外部钠来降低外部钠浓度,可抑制大鼠细胞动作电位的晚期阶段,并缩短豚鼠细胞动作电位的平台期。细胞内注入乙二醇双四乙酸(EGTA)可消除收缩,同时抑制大鼠细胞动作电位的晚期阶段,并缩短豚鼠细胞的平台期。雷尼丁(1微摩尔)被认为可抑制钙从内部储存库的释放,它可抑制大鼠细胞的收缩和动作电位的晚期阶段。在豚鼠细胞中,1微摩尔的雷尼丁对收缩或动作电位的时程没有实质性影响。将外部钾浓度增加到12毫摩尔可抑制大鼠细胞动作电位的晚期阶段,而将外部钾浓度降低到1.2毫摩尔则可增强该阶段。结论是,由内部钙激活的内向电流有助于大鼠细胞动作电位的晚期阶段以及豚鼠细胞的平台期。有两种可能性,一种是由电致钠钙交换产生的电流,另一种是通过钙激活的离子通道的电流。降低外部钠的影响与这两种机制中的任何一种都相符。预计这种内向电流的贡献会因通过整流钾电导的外向电流而改变,该电导随外部钾浓度而变化。在大鼠中,而非豚鼠中,激活内向电流的内部钙升高似乎很大程度上依赖于雷尼丁敏感的钙从内部储存库的释放。

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