Sham J S, Cleemann L, Morad M
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Medical School, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):121-5. doi: 10.1073/pnas.92.1.121.
In skeletal muscle, dihydropyridine receptors are functionally coupled to ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional complexes. In cardiac muscle direct physical or functional couplings have not been demonstrated. We have tested the hypothesis of functional coupling of L-type Ca2+ channels and ryanodine receptors in rat cardiac myocytes by comparing the efficacies of Ca2+ in triggering Ca2+ release when the ion enters the cell via the Ca2+ channels or the Na+/Ca2+ exchanger. Ca2+ transported through the Ca2+ channels was 20-160 times more effective than Ca2+ influx via the Na+/Ca2+ exchanger in gating Ca2+ release from the sarcoplasmic reticulum, suggesting privileged communication between Ca2+ channels and ryanodine receptors. In support of this hypothesis we found that Ca2+ channels were inactivated by Ca2+ release from the sarcoplasmic reticulum, even though the myoplasmic Ca2+ concentrations were buffered with 10 mM EGTA. The data thus suggest privileged cross signaling between the dihydropyridine and ryanodine receptors such that Ca2+ flux through either the Ca2+ channel or the ryanodine receptor alters the gating kinetics of the other channel.
在骨骼肌中，二氢吡啶受体在三联体或二联体连接复合体中与肌浆网的兰尼碱受体功能偶联。在心肌中，尚未证实存在直接的物理或功能偶联。我们通过比较钙离子经钙离子通道或钠/钙交换体进入细胞时触发钙离子释放的效率，来检验大鼠心肌细胞中L型钙离子通道与兰尼碱受体功能偶联的假说。经钙离子通道转运的钙离子在开启肌浆网钙离子释放方面比经钠/钙交换体的钙离子内流有效20 - 160倍，这表明钙离子通道与兰尼碱受体之间存在特殊的联系。为支持这一假说，我们发现即使肌浆内钙离子浓度用10 mM乙二醇双乙醚二胺四乙酸（EGTA）缓冲，肌浆网释放的钙离子仍可使钙离子通道失活。因此，数据表明二氢吡啶受体与兰尼碱受体之间存在特殊的交叉信号传递，使得通过钙离子通道或兰尼碱受体的钙离子通量会改变另一个通道的门控动力学。
