Physiological properties and functions of Ca2+ sparks in rat intrapulmonary arterial smooth muscle cells
Physiological properties and functions of Ca2+ sparks in rat intrapulmonary arterial smooth muscle cells
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DOI：
10.1152/ajplung.00468.2001
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发表时间：
2002-08-01
影响因子：
4.9
通讯作者：
Sham, JSK
中科院分区：
文献类型：
--
作者：
Remillard, CV;Zhang, WM;Sham, JSK
Ca ~（+）火花是系统动脉平滑肌细胞（SASMCs）膜电位和血管紧张性调节的重要反馈机制，但对肺动脉平滑肌细胞（PASMCs）的Ca ~（+）火花的性质知之甚少。利用共聚焦显微镜，我们确定自发性钙火花在大鼠肺动脉平滑肌细胞和其时空特性和生理功能。PASMCs的Ca ~（2+）火花频率和幅度均低于心脏火花。它们被废除的ryanodine受体的抑制，但不是通过抑制肌醇三磷酸受体和L-型Ca 2+通道。BAY K8644、K+或高Ca 2+可增强Ca 2+内流，导致火花频率显著增加。在功能上，增强Ca 2+火花与咖啡因（0.5 mM）引起膜去极化PASMCs，在SASMCs超极化。去甲肾上腺素和内皮素-1都引起细胞内Ca 2+浓度（[Ca 2 +]）的整体升高，但只有内皮素-1增加火花频率。这些结果表明，PASMCs的Ca ~（2+）火花与SASMCs的相似，起源于ryanodine受体，并被Ca ~（2+）内流增强。然而，它们对膜电位发挥不同的调节作用，并且在激动剂特异性调节下独立于全局[Ca 2 +]。
Ca+ spark has been implicated as a pivotal feedback mechanism for regulating membrane potential and vasomotor tone in systemic arterial smooth muscle cells (SASMCs), but little is known about its properties in pulmonary arterial smooth muscle cells (PASMCs). Using confocal microscopy, we identified spontaneous Ca2+ sparks in rat intralobar PASMCs and characterized their spatiotemporal properties and physiological functions. Ca2+ sparks of PASMCs had a lower frequency and smaller amplitude than cardiac sparks. They were abolished by inhibition of ryanodine receptors but not by inhibition of inositol trisphosphate receptors and L-type Ca2+ channels. Enhanced Ca2+ influx by BAY K8644, K+, or high Ca2+ caused a significant increase in spark frequency. Functionally, enhancing Ca2+ sparks with caffeine (0.5 mM) caused membrane depolarization in PASMCs, in contrast to hyperpolarization in SASMCs. Norepinephrine and endothelin-1 both caused global elevations in cytosolic Ca2+ concentration ([Ca2+]), but only endothelin-1 increased spark frequency. These results suggest that Ca2+ sparks of PASMCs are similar to those of SASMCs, originate from ryanodine receptors, and are enhanced by Ca2+ influx. However, they play a different modulatory role on membrane potential and are under agonist-specific regulation independent of global [Ca2+].