BETA-ADRENERGIC STIMULATION OF CALCIUM CHANNELS OCCURS BY POTENTIATION OF HIGH-ACTIVITY GATING MODES

BETA-ADRENERGIC STIMULATION OF CALCIUM CHANNELS OCCURS BY POTENTIATION OF HIGH-ACTIVITY GATING MODES
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DOI:
10.1073/pnas.87.2.753
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发表时间:
1990-01-01
影响因子:
11.1
通讯作者:
MARBAN, E
MARBAN, E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
YUE, DT;HERZIG, S;MARBAN, E

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camp依赖性磷酸化明显增加通过心脏l型Ca通道的电流,但这种作用的分子存在争议。先前的研究表明,要么是功能性通道数量的增加,要么是单个通道门控的梯度变化。我们现在发现单个心脏钙通道显示出三种活动模式(“模式”),异丙肾上腺素或8-溴腺苷3”,5”-环单磷酸重新分配了模式的相对比例,使两种最活跃的模式(模式1,短暂开放的爆发;模式2,非常持久的开放)更受青睐(p < 0.05; n = 7)。相反,稀疏的短暂开口模式(模式0a)被选择性地抑制(p < 0.01)。尽管在药物暴露之前和期间,各种模式的相对频率有所不同,但每种模式内的门控并没有明显的变化。我们得出结论,钙通道门控的高活性模式的增强是β增强钙内流的基础。肾上腺素的刺激。
cAMP-dependent phosphorylation clearly increases current through cardiac L-type Ca channels, but the molecular menifestation of this effect remains controversial. Previous work implicates either an increase in the number of functional channels or graded changes in the gating of individual channels. We now find that single cardiac Ca channels display three patterns of activity ("modes") and that isoproterenol or 8-bromoadenosine 3'',5''-cyclic monophosphate redistributes the relative proportions of modes such that the two most active (mode 1, bursts of brief openings; mode 2, very long-lasting openings) are favored (p < 0.05; n = 7). Conversely, a pattern of sparse brief openings (mode 0a) is selectively inhibited (p < 0.01). Despite differences in the relative frequencies of the various modes before and during drug exposure, the gating within each mode is not detectably changed. We conclude that potentiation of highly active modes of Ca channel gating underlies the enhancement of calcium influx by .beta.-adrenergic stimulation.