在分离的豚鼠心室心肌细胞中，蛋白激酶C的刺激对L型钙通道的抑制作用。

Inhibition in L-type Ca2+ channel by stimulation of protein kinase C in isolated guinea pig ventricular cardiomyocytes.

Satoh H

Department of Pharmacology, Nara Medical University, Japan.

Gen Pharmacol. 1992 Nov;23(6):1097-102. doi: 10.1016/0306-3623(92)90293-s.

Abstract

Electrophysiological effects of phorbol esters on the L-type Ca2+ current (ICa(L)) in isolated single ventricular cells from guinea pig hearts were investigated. 2. In whole-cell voltage-clamped myocytes, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) at 10(-7) M inhibited ICa(L). An antagonist of protein kinase C (PK-C), H-7, at 10(-5) M did not modify the TPA-induced inhibition. The time-course of inactivation process for ICa(L) was greatly slowed. 3. In cell-attached patch-clamp experiments, TPA (10(-7) M) also markedly decreased the opening of L-type Ca2+ channels. The conductance was unaffected. 4. Even H-7 (10(-5) M) alone inhibited the opening of the channels. Addition of TPA (10(-7)-10(-8) M) caused further decrease in the opening. 5. On the other hand, 4-alpha-phorbol-12,13-didecanoate (not a PK-C activator) had no effect on the Ca2+ channels. 6. These results indicate that the PK-C activation induced by TPA greatly depresses the opening of L-type Ca2+ channels in ventricular cell membranes.

摘要

研究了佛波酯对豚鼠心脏分离的单个心室细胞中L型钙电流（ICa(L)）的电生理效应。2. 在全细胞膜片钳记录的心肌细胞中，10(-7) M的12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）抑制ICa(L)。蛋白激酶C（PK - C）拮抗剂H - 7（10(-5) M）不改变TPA诱导的抑制作用。ICa(L)的失活过程时间进程显著减慢。3. 在细胞贴附式膜片钳实验中，TPA（10(-7) M）也显著减少L型钙通道的开放。电导不受影响。4. 即使单独使用H - 7（10(-5) M）也抑制通道开放。加入TPA（10(-7) - 10(-8) M）导致开放进一步减少。5. 另一方面，4 - α - 佛波醇 - 12,13 - 十二烷酸酯（不是PK - C激活剂）对钙通道无影响。6. 这些结果表明，TPA诱导的PK - C激活极大地抑制了心室细胞膜中L型钙通道的开放。