Bean B P, Nowycky M C, Tsien R W
Nature. 1984;307(5949):371-5. doi: 10.1038/307371a0.
Adrenergic modulation of calcium channels profoundly influences cardiac function, and has served as a prime example of neurohormonal regulation of voltage-gated ion channels. Channel modulation and increased Ca influx are mediated by elevation of intracellular cyclic AMP and protein phosphorylation. The molecular mechanism of the augmented membrane Ca conductance has attracted considerable interest. An increase in the density of functional channels has often been proposed, but there has previously been no direct evidence. Single-channel recordings show that isoprenaline or 8-bromocyclic AMP increase the proportion of time individual channels spend open by prolonging openings and shortening the closed periods between openings. To look for an additional contribution of changes in the number of functional channels, we applied ensemble fluctuation analysis to whole-cell recordings of cardiac Ca channel activity. Here we present evidence that in frog ventricular heart cells beta-adrenergic stimulation increases NF, the average number of functional Ca channels per cell. We also find that isoprenaline slows the time course of both activation and inactivation, and that the enhancement of peak current decreases gradually with greater membrane depolarization.
肾上腺素能对钙通道的调节深刻影响心脏功能，并且一直是神经激素对电压门控离子通道调节的一个主要例子。通道调节和钙内流增加是由细胞内环磷酸腺苷（cAMP）水平升高和蛋白质磷酸化介导的。膜钙电导增加的分子机制引起了相当大的关注。人们常常提出功能性通道密度增加，但以前没有直接证据。单通道记录表明，异丙肾上腺素或8-溴环磷酸腺苷通过延长开放时间和缩短开放之间的关闭期，增加了单个通道开放所花费的时间比例。为了寻找功能性通道数量变化的额外作用，我们将整体涨落分析应用于心脏钙通道活性的全细胞记录。在此我们提供证据表明，在蛙心室肌细胞中，β肾上腺素能刺激增加了NF，即每个细胞中功能性钙通道的平均数量。我们还发现，异丙肾上腺素减慢了激活和失活的时间进程，并且随着膜去极化程度的增加，峰值电流的增强逐渐减弱。
