β-adrenergic stimulation modulates Ca2+- and voltage-dependent inactivation of L-type Ca2+ channel currents in guinea-pig ventricular myocytes
β-adrenergic stimulation modulates Ca2+- and voltage-dependent inactivation of L-type Ca2+ channel currents in guinea-pig ventricular myocytes
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DOI：
10.1113/jphysiol.2002.019737
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发表时间：
2002-06-15
影响因子：
5.5
通讯作者：
Findlay, I
中科院分区：
文献类型：
--
作者：
Findlay, I
本研究的目的是研究β-肾上腺素能刺激对电压和Ca 2+诱导的天然心脏L-型Ca 2+通道失活的影响。从豚鼠分离的心室肌细胞记录全细胞电流。总的和电压依赖性的失活被分开，用Mg 2+替代细胞外Ca 2+。L-型Ca 2+通道行为与外向Ca 2+通道电流监测。首先，在活化后的固定时间（50和1000 ms）研究了失活的电压依赖性。这表明在对照条件下，Ca 2+对失活的贡献很小。在异丙肾上腺素中，电压依赖性失活显著减少，Ca 2+在很大程度上促进了总失活。其次，在固定电压（+10 mV）下研究了灭活的时间依赖性。在对照条件下，灭活的快相（tau（f）类似于15 ms）被ryanodine（tau（f）类似于30 ms）和不存在Ca 2+（tau（f）类似于30 ms）降低到相同程度，而灭活的慢相（tau（s）类似于70 ms）被ryanodine（tau（s）类似于160 ms）降低，并且在不存在Ca 2+（τ（s）类似于300 ms）。在异丙肾上腺素中，在不存在Ca 2+的情况下，Ca 2+电流的双相失活（tau（f）类似于4 ms，tau（s）类似于60 ms）被单个缓慢失活（tau类似于450 ms）相取代。它的结论是，在控制条件下的Ca 2+通道电流衰减主要是由快速电压依赖性失活，而在异丙肾上腺素这是由Ca 2+诱导的失活取代。
The objective of this study was to examine the effect of beta-adrenergic stimulation upon voltage- and Ca2+-induced inactivation of native cardiac L-type Ca2+ channels. Whole-cell currents were recorded from guinea-pig isolated ventricular myocytes. Total and voltage-dependent inactivation was separated by replacing extracellular Ca2+ with Mg2+. L-type Ca2+ channel behaviour was monitored with outward Ca2+ channel currents. First, the voltage dependence of inactivation was studied at fixed times (50 and 1000 ms) after activation. This showed that under control conditions Ca2+ contributed little to inactivation. In isoproterenol (isoprenaline), voltage- dependent inactivation was markedly reduced and Ca2+ contributed largely to total inactivation. Second, the time dependence of inactivation was studied at a fixed voltage (+10 mV). In control conditions the fast phase of inactivation (tau(f) similar to 15 ms) was reduced to the same extent by ryanodine(tau(f) similar to 30 ms) and the absence of Ca2+ (tau(f) similar to 30 ms) while the slow phase of inactivation (tau(s) similar to 70 ms) was reduced by ryanodine (tau(s) similar to 160 ms) and further reduced in the absence of Ca2+ (tau(s) similar to 300 ms). In isoproterenol, biphasic inactivation of Ca2+ currents (tau(f) similar to 4 ms, tau(s) similar to 60 ms) was replaced by a single slow (tau similar to 450 ms) phase of inactivation in the absence of Ca2+. It is concluded that, under control conditions Ca2+ channel current decay is largely dominated by rapid voltage-dependent inactivation, while in isoproterenol this is replaced by Ca2+-induced inactivation.