BETA-ADRENERGIC MODULATION OF CALCIUM CHANNELS IN FROG VENTRICULAR HEART-CELLS
BETA-ADRENERGIC MODULATION OF CALCIUM CHANNELS IN FROG VENTRICULAR HEART-CELLS
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DOI：
10.1038/307371a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
TSIEN, RW
中科院分区：
文献类型：
--
作者：
BEAN, BP;NOWYCKY, MC;TSIEN, RW
钙通道的肾上腺素能调节深刻地影响心脏功能1，2，并已作为电压门控离子通道1 -7的神经激素调节的一个主要例子。通道调节和增加的Ca流入2，8，9是由细胞内环AMP 10 - 17和蛋白磷酸化18，19的升高介导的。膜钙电导增加的分子机制引起了人们的极大兴趣。功能通道密度的增加经常被提出20 -22，但以前没有直接的证据。单通道记录表明，异丙肾上腺素或8-溴环AMP增加的时间比例个别通道花开放延长开口和缩短之间openings 2，23-25关闭期。为了寻找功能通道数量变化的额外贡献，我们将系综波动分析26应用于心脏Ca通道活动的全细胞记录27，28。在这里，我们提出的证据表明，在青蛙心室心肌细胞β-肾上腺素能刺激增加NF，每个细胞的功能性钙通道的平均数量。我们还发现，异丙肾上腺素减慢激活和失活的时间过程中，和增加的峰值电流逐渐减少与更大的膜去极化。
Adrenergic modulation of calcium channels profoundly influences cardiac function1,2, and has served as a prime example of neurohormonal regulation of voltage-gated ion channels1–7. Channel modulation and increased Ca influx2,8,9are mediated by elevation of intracellular cyclic AMP10–17and protein phosphorylation18,19. The molecular mechanism of the augmented membrane Ca conductance has attracted considerable interest. An increase in the density of functional channels has often been proposed20–22, 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 openings2,23–25. To look for an additional contribution of changes in the number of functional channels, we applied ensemble fluctuation analysis26to whole-cell recordings27,28of cardiac Ca channel activity. Here we present evidence that in frog ventricular heart cellsβ-adrenergic stimulation increasesNF, 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.