Mechanism of substance P-induced hyperpolarization of porcine coronary artery endothelial cells.
Mechanism of substance P-induced hyperpolarization of porcine coronary artery endothelial cells.
复制标题
P物质诱导猪冠状动脉内皮细胞超极化的机制。
DOI：
10.1152/ajpheart.1994.266.1.h156
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Davis,MJ
中科院分区：
文献类型：
--
作者：
Sharma,NR;Davis,MJ
P物质（SP）是一种有效的内皮依赖性血管扩张剂，在猪冠状动脉中，SP的血管扩张作用似乎完全由一氧化氮介导。我们验证了SP通过激活Ca（2+）激活的K+（KCa）通道诱导猪冠状动脉内皮细胞（PCAECs）超极化的假设。在1 mM的浴钙浓度（[Ca 2 +]）下，10 nM SP引起细胞溶质[Ca 2 +]（[Ca 2 +]i）从基线25 +/- 4 nM增加至峰值808 +/- 120 nM，随后出现缓慢下降的平台期，该平台期在无Ca（2+）浴中不存在，并通过添加细胞外镧或镍消除。全细胞电流钳记录显示，SP诱导的[Ca 2 +]i增加的时间过程与膜超极化密切相关，从平均静息电位-42 +/- 2到峰值-79 +/- 2 mV。在电压钳下，SP刺激全细胞电流，其逆转电位强烈依赖于细胞外K+浓度。在62%的测试补丁，单通道记录显示一个中间电导K+通道与激活高度相关的SP诱导的[Ca 2 +]i增加。这些结果表明，在PCAECs中，SP诱导钙库释放Ca 2+沿着Ca 2+内流，激活KCa通道，导致超极化。这可能会增加Ca 2+进入的驱动力，从而调节内皮源性一氧化氮的释放。
Substance P (SP) is a potent endothelium-dependent vasodilator, and in porcine coronary arterioles the vasodilatory action of SP appears to be mediated entirely by nitric oxide. We tested the hypothesis that SP induces hyperpolarization in porcine coronary artery endothelial cells (PCAECs) by activating Ca(2+)-activated K+ (KCa) channels. With a bath Ca2+ concentration ([Ca2+]) of 1 mM, 10 nM SP elicited an increase in cytosolic [Ca2+] ([Ca2+]i) from a baseline of 25 +/- 4 nM to a peak of 808 +/- 120 nM, followed by a slowly declining plateau phase, which was absent in Ca(2+)-free bath and was abolished by addition of extracellular lanthanum or nickel. Whole cell current-clamp recordings revealed that the time course of SP-induced [Ca2+]i increases correlated closely with membrane hyperpolarization from an average resting potential of -42 +/- 2 to a peak of -79 +/- 2 mV. Under voltage clamp, SP stimulated whole cell currents with reversal potentials strongly dependent on extracellular K+ concentration. In 62% of patches tested, single-channel recordings revealed an intermediate-conductance K+ channel with activation highly correlated with the SP-induced [Ca2+]i increase. These results suggest that, in PCAECs, SP induces Ca2+ release from stores along with Ca2+ influx which activate a KCa channel leading to hyperpolarization. This may increase the driving force for Ca2+ entry and thus modulate endothelium-derived nitric oxide release.