Voltage‐ and Use‐Dependent Modulation of Cardiac Calcium Channels by the Dihydropyridine (+)‐202‐791
Voltage‐ and Use‐Dependent Modulation of Cardiac Calcium Channels by the Dihydropyridine (+)‐202‐791
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二氢吡啶 (+)-202-791 对心脏钙通道的电压和使用依赖性调节
DOI：
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发表时间：
1989
影响因子：
20.1
通讯作者：
Richard J. Miller
中科院分区：
文献类型：
--
作者：
T. Kamp;M. Sanguinetti;Richard J. Miller
采用全细胞电压钳技术，以1.8 mM Ba或Ca为电荷载体，研究了二氢吡啶(+)-202-791对离体豚鼠心室肌细胞l型电压敏感钙通道的调制作用。揭示了二氢吡啶钙通道激动剂(+)-202-791的显著电压依赖性和使用依赖性效应。在保持电位为-60 mV时，与对照相比，(+)-202-791存在下的去极化测试脉冲显示出浓度依赖性（EC50, 177 nM），测量到的峰值向内钡电流增加。相反，更多的去极化保持电位（±- 30mv）(+)-202-791对峰值内向电流产生双相效应，导致瞬态增强，随后是稳态阻滞。在(+)-202-791的存在下，观察到电流失活的电压依赖性中存在饱和的、浓度依赖性的超极化位移，EC50为10.2 nM。在(+)-202-791的存在下，电流激活的电压依赖性也向超极化方向偏移。在频率为2hz的重复去极化测试脉冲后，观察到(+)-202-791的使用依赖相对阻滞。因此，单一对映体(+)-202-791可以导致全细胞钙通道电流的增加（有利于超极化保持电位和低刺激率）或钙通道电流的阻断（有利于去极化保持电位和高刺激率）。（-）-202-791（一种钙通道拮抗剂）和(+)-202-791的各种组合与单独存在的对映体相比，对电压敏感的钙或钡电流产生了中间效应，并且与先前的单通道研究（Kokuban S, Prod'ham B, Becker C, Porzig H, Reuter H）相比，未观察到对映体之间明显的协同相互作用。二氢吡啶对映体的电压依赖效应和协同相互作用。Mol Pharmacol 1986；30: 571 - 584)。结果讨论了与电压敏感钙通道相关的多个二氢吡啶受体可能存在的关系。
The modulation of L-type voltage sensitive calcium channels in isolated guinea pig ventricular myocytes by the dihydropyridine (+)-202-791 was examined with the whole-cell voltage-clamp technique with 1.8 mM Ba or Ca as the charge carrier. Striking voltage- and use-dependent effects of the dihydropyridine calcium channel "agonist" (+)-202-791 were revealed. From a holding potential of -60 mV, depolarizing test pulses in the presence of (+)-202-791 demonstrated a concentration-dependent (EC50, 177 nM) increase in the measured peak inward barium current compared to control. In contrast, more depolarized holding potentials (±-30 mV) (+)-202-791 caused a biphasic effect on the peak inward current resulting in a transient enhancement followed by a steady-state block. A saturable, concentration-dependent hyperpolarizing shift in the voltage dependence of current inactivation was observed in the presence of (+)-202-791 with an EC50 of 10.2 nM. The voltage dependence of current activation was also shifted in the hyperpolarizing direction in the presence of (+)-202-791. A use-dependent relative block by (+)-202-791 was observed after repetitive depolarizing test pulses at a frequency of 2 Hz. Thus, the single enantiomer (+)-202-791 can result in either an increase in the whole cell calcium channel current (favored by hyperpolarized holding potentials and low rates of stimulation) or block of calcium channel current (favored by depolarized holding potentials and high rates of stimulation). Various combinations of (-)-202-791, a reported calcium channel antagonist, and (+)-202-791 resulted in intermediate effects on voltage sensitive calcium or barium currents compared with the presence of either enantiomer alone, and no clear cooperative interactions between the enantiomers were observed in contrast to a previous single channel study (Kokuban S, Prod'ham B, Becker C, Porzig H, Reuter H: Studies on Ca channels in intact cardiac cells: Voltage-dependent effects and cooperative interaction of dihydropyridine enantiomers. Mol Pharmacol 1986; 30: 571-584). The results are discussed in relation to the possible presence of multiple dihydropyridine receptors associated with the voltage sensitive calcium channel.
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二氢吡啶 202-791 立体异构体的钙通道激动剂和拮抗剂作用。
DOI：
10.1016/0006-291x(85)90393-6
发表时间：
1985
影响因子：
3.1
作者：
Kongsamut,S;Kamp,TJ;Miller,RJ;Sanguinetti,MC
通讯作者：
Sanguinetti,MC
心脏制剂中二氢吡啶 202-791 的相反作用对映体的概况：受体结合、电生理学和药理学研究。
DOI：
10.1016/0006-291x(85)91763-2
发表时间：
1985
影响因子：
3.1
作者：
Williams,JS;Grupp,IL;Grupp,G;Vaghy,PL;Dumont,L;Schwartz,A;Yatani,A;Hamilton,S;Brown,AM
通讯作者：
Brown,AM
Bay K 8644 光学异构体对心脏钙通道电流的电压依赖性调节：对通道门控的影响。
影响因子：
20.1
作者：
Kass,RS
通讯作者：
Kass,RS
二氢吡啶对心脏膜的结合和电生理效应的比较。
影响因子：
3.6
作者：
Hamilton,SL;Yatani,A;Brush,K;Schwartz,A;Brown,AM
通讯作者：
Brown,AM
电压依赖性尼群地平与心脏肌膜囊泡的结合。
影响因子：
3.6
作者：
Kamp,TJ;Miller,RJ
通讯作者：
Miller,RJ