Intracellular regulation of Ca^<2+> release from cardiac sarcoplasmic reticulum.

通过记录单通道电流，研究了心肌肌浆网离子通道的调节机制：(1)发现心肌肌浆网(SR)存在氯离子通道，该通道被环磷酸腺苷(CAMP)依赖的磷酸化激活，并被钙离子/钙调素复合体抑制。这些都是细胞内通道调节的新证据。我发表了关于这些证据的论文(《循环研究》，1993)。(2)SR的Ryanodine受体钙释放通道(RyR)对细胞内钙的供应起着重要作用。我们通过记录RyR的单通道活动来研究RyR的调节机制，发现蝎子毒素可以促进这些通道的开放，这可能是Ryanodine受体的新型激动剂。钙拮抗剂维拉帕米可直接阻断兰尼定受体通道的开放，从而减少心脏的收缩。我详细介绍了镁离子对肌质网钙释放的调节机制。(2)细胞内钙由肌浆网提供，对细胞功能起着重要作用。我发现心肌细胞膜上存在钙激活的C_1通道，并通过细胞内钙激活该通道的具体机制进行了研究。这篇论文现已在伦敦的《生理学杂志》上发表。我需要研究这个氯离子通道的进一步调节机制。

I have investigated the regulatory mechanism of ion channels in cardiac sarcoplasmic reticulum by recording single channel currents.(1) I found that Cl-channel existed in cardiac sarcoplasmic reticulum (SR) and that this channel was activated by cyclic AMP-dependent phosphorylation and was inhibited by Ca^<2+>/calmodulin complex. These are new evidences of intracellular channel regulations. I published the paper about these evidences (Circulation Research, 1993). (2) Ryanodine receptor Ca^<2+> release channel (RyR) in SR playd the important role for Ca^<2+> supply in the cells. We examined the regulatory mechanisms of RyR by recordingsingle channel activities and found that these channel openings were enhanced by scorpion toxin, which might be the new type of activator for ryanodine receptor. Ca^<2+> antagonist, verapamil, blocked ryanodine receptor channel openings directly to reduce the contraction of the heart. I showed the detail regulatory mechanisms of Ca^<2+> release from SR by Mg^<2+>.(2) Intracellular Ca^<2+> is supplied from SR and plays many important roles for cell functions. I found that cardiac sarcolemma had Ca^<2+> -activated C1-channel and examined the detail activation mechanisms of this channel by intracellular Ca^<2+>. This paper is now in press of Journal of Physiology in London. I need to study the further regulatory mechanisms of this Cl-channel.