Zhou Z, January C T
Department of Medicine, The University of Wisconsin, Madison 53792, USA.
Biophys J. 1998 Apr;74(4):1830-9. doi: 10.1016/S0006-3495(98)77893-2.
Although L-type Ca2+ channels have been shown to play a central role in cardiac excitation-contraction (E-C) coupling, little is known about the role of T-type Ca2+ channels in this process. We used the amphotericin B perforated patch method to study the possible role of T-type Ca2+ current in E-C coupling in isolated canine Purkinje myocytes where both Ca2+ currents are large. T-type Ca2+ current was separated from L-type Ca2+ current using protocols employing the different voltage dependencies of the channel types and their different sensitivities to pharmacological blockade. We showed that Ca2+ admitted through either T- or L-type Ca2+ channels is capable of initiating contraction and that the contractions depended on Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR). The contractions, however, had different properties. Those initiated by Ca2+ entry through T-type Ca2+ channels had a longer delay to the onset of shortening, slower rates of shortening and relaxation, lower peak shortening, and longer time to peak shortening. These differences were present even when L-type Ca2+ current amplitude, or charge entry, was less than that of T-type Ca2+ current, suggesting that Ca2+ entry through the T-type Ca2+ channel is a less effective signal transduction mechanism to the SR than is Ca2+ entry through the L-type Ca2+ channel. We conclude that under our experimental conditions in cardiac Purkinje cells Ca2+ entry through the T-type Ca2+ channel can activate cell contraction. However, Ca2+ entry through the L-type Ca2+ channel is a more effective signal transduction mechanism. Our findings support the concept that different structural relationships exist between these channel types and the SR Ca2+ release mechanism.
尽管L型钙通道已被证明在心脏兴奋-收缩（E-C）偶联中起核心作用，但关于T型钙通道在此过程中的作用却知之甚少。我们采用两性霉素B穿孔膜片钳方法，研究T型钙电流在分离的犬浦肯野心肌细胞E-C偶联中的可能作用，在这些细胞中两种钙电流都很大。利用通道类型的不同电压依赖性及其对药物阻断的不同敏感性的实验方案，将T型钙电流与L型钙电流分离。我们发现，通过T型或L型钙通道进入的Ca2+都能够引发收缩，并且这些收缩依赖于肌浆网（SR）的钙诱导钙释放。然而，这些收缩具有不同的特性。由Ca2+通过T型钙通道进入引发的收缩，到缩短开始的延迟更长，缩短和舒张速率更慢，峰值缩短更低，达到峰值缩短的时间更长。即使L型钙电流幅度或电荷进入量小于T型钙电流，这些差异仍然存在，这表明Ca2+通过T型钙通道进入对SR来说是一种比Ca2+通过L型钙通道进入效率更低的信号转导机制。我们得出结论，在我们对心脏浦肯野细胞的实验条件下，Ca2+通过T型钙通道进入可激活细胞收缩。然而，Ca2+通过L型钙通道进入是一种更有效的信号转导机制。我们的研究结果支持了这样一种概念，即这些通道类型与SR钙释放机制之间存在不同的结构关系。
