期刊
CELL CALCIUM
卷 43, 期 2, 页码 122-141出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2007.04.012
关键词
smooth muscle cells; muscarinic receptors; IP3 receptors; ryanodine receptors; confocal microscopy; Ca2+-induced Ca2+ release; E-C coupling
类别
资金
- British Heart Foundation [FS/04/052, FS/06/077] Funding Source: Medline
- Wellcome Trust [075112, 074724, 042293] Funding Source: Medline
Membrane depolarization triggers Ca2+ release from the sarcoplasmic reticulum (SR) in skeletal muscles via direct interaction between the voltage-gated L-type Ca2+ channels (the dihydropyridine receptors; VGCCs) and ryanodine receptors (RyRs), while in cardiac muscles Ca2+ entry through VGCCs triggers RyR-mediated Ca2+ release via a Ca2+-induced Ca2+ release (CICR) mechanism. Here we demonstrate that in phasic smooth muscle of the guinea-pig small intestine, excitation evoked by muscarinic receptor activation triggers an abrupt Ca2+ release from sub-plasmalemmal (sub-PM) SR elements enriched with inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and poor in RyRs. This was followed by a lesser rise, or oscillations in [Ca2+](i). The initial abrupt sub-PM [Ca2+](i) upstroke was all but abolished by block of VGCCs (by 5 mu M nicardipine), depletion of intracellular Ca2+ stores (with 10 mu M cyclopiazonic acid) or inhibition Of IP(3)Rs (by 2 mu M xestospongin C or 30 mu M 2-APB), but was not affected by block of RyRs (by 50-100 mu M tetracame or 100 mu M ryanodine). Inhibition of either IP(3)Rs or RyRs attenuated phasic muscarinic contraction by 73%. Thus, in contrast to cardiac muscles, excitation-contraction coupling in this phasic visceral smooth muscle occurs by Ca2+ entry through VGCCs which evokes an initial IP3R-mediated Ca2+ release activated via a CICR mechanism. (C) 2007 Elsevier Ltd. All rights reserved.
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