NOVEL MECHANISM OF VOLTAGE-DEPENDENT GATING IN L-TYPE CALCIUM CHANNELS
NOVEL MECHANISM OF VOLTAGE-DEPENDENT GATING IN L-TYPE CALCIUM CHANNELS
复制标题
DOI：
10.1038/346651a0
复制
发表时间：
1990-08-16
期刊：
影响因子：
64.8
通讯作者：
HESS, P
中科院分区：
文献类型：
--
作者：
PIETROBON, D;HESS, P
通过膜去极化激活电压依赖性钙通道会触发各种关键的细胞反应，例如心脏和平滑肌的收缩以及内分泌和神经细胞的胞吐分泌。钙通道门控的调节被认为是多种神经递质、激素和治疗剂介导其对细胞功能的影响的机制。在这里，我们描述了二氢吡啶敏感（L 型）心脏 Ca2+ 通道的不同门控模式之间的一种新型电压依赖性平衡。强去极化驱动通道从正常的门控模式进入以长开口和高开放概率为特征的门控模式1,2。根据单通道记录估计的门控模式之间转换的速率常数比正常通道打开和关闭速率慢得多，但模式之间的平衡几乎与更负电势下的通道激活和失活一样陡峭地依赖于电压。这种电压依赖性门控的新机制可以解释先前关于心脏3和其他细胞2,4,5中活性依赖性Ca2+通道增强的报道，并形成一种可以调节细胞内Ca2+摄取的有效机制。
ACTIVATION of voltage-dependent calcium channels by membrane depolarization triggers a variety of key cellular responses, such as contraction in heart and smooth muscle and exocytotic secretion in endocrine and nerve cells. Modulation of calcium channel gating is believed to be the mechanism by which several neurotransmitters, hormones and therapeutic agents mediate their effects on cell function. Here we describe a novel type of voltage-dependent equilibrium between different gating patterns of dihy-dropyridine-sensitive (L-type) cardiac Ca2+channels. Strong depolarizations drive the channel from its normal gating pattern into a mode of gating characterized by long openings and high open probability1,2. The rate constants for conversions between gating modes, estimated from single channel recordings, are much slower than normal channel opening and closing rates, but the equilibrium between modes is almost as steeply voltage-dependent as channel activation and deactivation at more negative potentials. This new mechanism of voltage-dependent gating can explain previous reports of activity-dependent Ca2+channel potentiation in cardiac3and other cells2,4,5and forms a potent mechanism by which Ca2+uptake into cells could be regulated.