Gilbert J C, Shirayama T, Pappano A J
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030.
Circ Res. 1991 Dec;69(6):1632-9. doi: 10.1161/01.res.69.6.1632.
An early inward tail current evoked by membrane depolarization (from -80 to -40 mV) sufficient to activate sodium but not calcium current was studied in single voltage-clamped ventricular myocytes isolated from guinea pig hearts. Like forward-mode Na-Ca exchange, this early inward tail current required [Na+]o and [Ca2+]i and is thought to follow earlier reverse-mode Na-Ca exchange that triggers Ca2+ release from sarcoplasmic reticulum. The dependence of the early inward tail current on [Ca2+]i was supported by the ability of small (+10 mV) and large (+80 mV) voltage jumps from -40 mV to decrease and increase, respectively, the size of early inward tail currents evoked by subsequent voltage steps from -80 to -40 mV. As expected, tetrodotoxin selectively inhibited the early inward tail current but not the late inward tail current that followed voltage jumps to +40 mV test potentials. Although tetrodotoxin also blocked the fast Na+ current, replacement of extracellular Na+ by Li+ sustained the fast Na+ current. However, Li+, which does not support Na-Ca exchange, reversibly suppressed both the early and late inward tail currents. Inhibitors (ryanodine and caffeine) and promoters (intracellularly dialyzed inositol 1,4,5-trisphosphate) of sarcoplasmic reticulum Ca2+ release decreased and increased, respectively, the magnitude of the early inward tail current. The results substantiate the hypothesis that Ca2+ release from the sarcoplasmic reticulum participates in early Na-Ca exchange current and demonstrate that inositol 1,4,5-trisphosphate, by releasing Ca2+ from the sarcoplasmic reticulum, can promote Na-Ca exchange across the plasma membrane.
在从豚鼠心脏分离的单个电压钳制心室肌细胞中，研究了由膜去极化（从-80 mV至-40 mV）诱发的早期内向尾电流，该去极化足以激活钠电流但不足以激活钙电流。与正向模式的钠钙交换一样，这种早期内向尾电流需要细胞外[Na⁺]和细胞内[Ca²⁺]，并且被认为是跟随早期的反向模式钠钙交换，后者触发肌浆网释放Ca²⁺。早期内向尾电流对[Ca²⁺]i的依赖性得到了如下事实的支持：从-40 mV进行小幅度（+10 mV）和大幅度（+80 mV）电压跃变，分别会降低和增加随后从-80 mV到-40 mV电压阶跃诱发的早期内向尾电流的大小。正如预期的那样，河豚毒素选择性抑制早期内向尾电流，但不抑制电压跃变至+40 mV测试电位后出现的晚期内向尾电流。尽管河豚毒素也阻断快速钠电流，但用Li⁺替代细胞外Na⁺可维持快速钠电流。然而，不支持钠钙交换的Li⁺可逆地抑制早期和晚期内向尾电流。肌浆网Ca²⁺释放的抑制剂（ryanodine和咖啡因）和促进剂（细胞内透析的肌醇1,4,5-三磷酸）分别降低和增加早期内向尾电流的幅度。这些结果证实了肌浆网释放Ca²⁺参与早期钠钙交换电流的假说，并证明肌醇1,4,5-三磷酸通过从肌浆网释放Ca²⁺，可促进质膜上的钠钙交换。
