Stretch-induced calcium release in smooth muscle.

Stretch-induced calcium release in smooth muscle.
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拉伸诱导的平滑肌钙释放。

DOI:
10.1085/jgp.20028514
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发表时间:
2002-06
期刊:
The Journal of general physiology
影响因子:
--
通讯作者:
Kotlikoff MI
Kotlikoff MI
中科院分区:
其他
文献类型:
--
作者:
Ji G;Barsotti RJ;Feldman ME;Kotlikoff MI

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平滑肌细胞的长度大幅增加,在血管和中空器官的腔内压力增加时被动拉伸。大约一个世纪前首次描述了抵消增加的跨壁压力的主动收缩反应,并且已经提出了几种机制来解释这种现象。我们在此报告,平滑肌细胞的伸长导致单个肌细胞中兰尼碱受体介导的 Ca2+ 释放。将分离的单个膀胱肌细胞机械伸长至松弛长度的 120% (ΔL = 20),引起细胞内储存的 Ca2+ 以单个 Ca2+ 火花和传播 Ca2+ 波的形式释放。 Ca2+ 释放不是由于钙诱导的钙释放,因为在不含 Ca2+ 的细胞外溶液中以及当细胞质中的游离 Ca2+ 离子被强烈缓冲以防止 [Ca2+]i 增加时观察到释放。拉伸诱导的钙释放 (SICR) 不受 InsP3R 介导的 Ca2+ 释放抑制的影响,但被兰尼定完全阻断。释放发生在没有先前报道的拉伸激活电流的情况下;然而,SICR 以瞬时内向电流的形式诱发钙激活的氯电流,这表明平滑肌中自发电流产生的调节机制。在完整膀胱平滑肌节段的拉伸过程中,在单个肌细胞中也观察到了 SICR。因此,平滑肌细胞的纵向拉伸通过 RYR 门控诱导 Ca2+ 释放。 SICR 可能是平滑肌组织中对管腔压力增加的生理反应的重要组成部分。
Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor–mediated Ca2+ release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to ∼120% of slack length (ΔL = 20) evoked Ca2+ release from intracellular stores in the form of single Ca2+ sparks and propagated Ca2+ waves. Ca2+ release was not due to calcium-induced calcium release, as release was observed in Ca2+-free extracellular solution and when free Ca2+ ions in the cytosol were strongly buffered to prevent increases in [Ca2+]i. Stretch-induced calcium release (SICR) was not affected by inhibition of InsP3R-mediated Ca2+ release, but was completely blocked by ryanodine. Release occurred in the absence of previously reported stretch-activated currents; however, SICR evoked calcium-activated chloride currents in the form of transient inward currents, suggesting a regulatory mechanism for the generation of spontaneous currents in smooth muscle. SICR was also observed in individual myocytes during stretch of intact urinary bladder smooth muscle segments. Thus, longitudinal stretch of smooth muscle cells induces Ca2+ release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.
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