VOLTAGE-DEPENDENT POTENTIATION OF L-TYPE CA2+ CHANNELS DUE TO PHOSPHORYLATION BY CAMP-DEPENDENT PROTEIN-KINASE
VOLTAGE-DEPENDENT POTENTIATION OF L-TYPE CA2+ CHANNELS DUE TO PHOSPHORYLATION BY CAMP-DEPENDENT PROTEIN-KINASE
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DOI：
10.1038/364240a0
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发表时间：
1993-07-15
期刊：
影响因子：
64.8
通讯作者：
CATTERALL, WA
中科院分区：
文献类型：
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作者：
SCULPTOREANU, A;SCHEUER, T;CATTERALL, WA
通过改变运动神经元的放电率，骨骼肌运动单位的收缩力分级，胞质钙瞬变也同样增加。在单次抽搐期间，收缩不依赖于细胞外钙3，并且L型Ca 2+通道可能仅用作启动肌浆网释放Ca 2+的电压传感器4 -6。相比之下，由动作电位在高频（20至200 Hz）触发的有力强直收缩依赖于细胞外Ca 2+浓度并且对L型Ca 2+通道拮抗剂敏感7 -9，但收缩力的调节机制尚不清楚。在这里，我们报告了一个大的，电压和频率依赖性增强骨骼肌L-型钙离子电流的列车的高频去极化预脉冲，这是由于在电压依赖性的通道激活更负的膜电位的转变，需要磷酸化的环AMP依赖性蛋白激酶在电压依赖性的方式。这种增强作用将显著增加骨骼肌纤维对强直刺激的反应中的Ca 2+内流和收缩力。
THE force of contraction of motor units in skeletal muscle is graded by changing the discharge rate of motor neurons1, and cytosolic calcium transients are similarly increased2. During single twitches, contraction is not dependent on extracellular calcium3, and L-type Ca2+ channels may only function as voltage sensors for initiating Ca2+ release from the sarcoplasmic reticulum4-6. In contrast, forceful tetanic contractions triggered by action potentials at high frequency (20 to 200 Hz) are dependent on extracellular Ca2+ concentration and sensitive to L-type Ca2+ channel antagonists7-9, but the mechanism of regulation of contractile force is unknown. Here we report a large, voltage- and frequency-dependent potentiation of skeletal muscle L-type Ca2+ currents by trains of high-frequency depolarizing prepulses, which is caused by a shift in the voltage-dependence of channel activation to more negative membrane potentials and requires phosphorylation by cyclic AMP-dependent protein kinase in a voltage-dependent manner. This potentiation would substantially increase Ca2+ influx and contractile force in skeletal muscle fibres in response to tetanic stimuli.