Neely A, Olcese R, Baldelli P, Wei X, Birnbaumer L, Stefani E
Department of Molecular Physiology, Baylor College of Medicine, Houston, Texas 77030.
Am J Physiol. 1995 Mar;268(3 Pt 1):C732-40. doi: 10.1152/ajpcell.1995.268.3.C732.
Ca2+ channels are heteromultimeric proteins in which the alpha 1-subunit forms the voltage-dependent Ca(2+)-selective ionic channel. We reported recently that coexpression of the beta-subunit with the cardiac alpha 1-subunit (alpha 1C) facilitates channel opening without affecting either the amplitude or the time course of the gating currents (13). Here we present evidence for the existence of two modes of channel opening. Xenopus oocytes expressing the alpha 1C-subunit alone display two modes of activation as indicated by the double-exponential time course of macroscopic ionic currents and the two open-time distributions of single channels. Coexpression of the beta-subunit potentiates Ca2+ currents by a relative increase of the fast-activating component, an acceleration of the slow component, and a larger proportion of long openings. We propose that multiple modes of gating are encoded in the alpha 1-subunit and that the beta-subunit increases Ca2+ channel opening by favoring a willing mode of gating in which the final transitions leading to channel opening are facilitated. In addition, we show that the carboxy terminus of alpha 1C also modulates the channel-gating behavior.
钙离子通道是异源多聚体蛋白，其中α1亚基形成电压依赖性钙选择性离子通道。我们最近报道，β亚基与心脏α1亚基（α1C）共表达可促进通道开放，而不影响门控电流的幅度或时程（13）。在此，我们提供了通道开放存在两种模式的证据。单独表达α1C亚基的非洲爪蟾卵母细胞表现出两种激活模式，这由宏观离子电流的双指数时程和单通道的两种开放时间分布表明。β亚基的共表达通过快速激活成分的相对增加、慢速成分的加速以及更长开放比例的增加来增强钙电流。我们提出，多种门控模式编码在α1亚基中，并且β亚基通过促进一种有利的门控模式来增加钙离子通道开放，在这种门控模式中，导致通道开放的最终转变更容易发生。此外，我们表明α1C的羧基末端也调节通道门控行为。
