Gordienko D V, Harhun M I, Kustov M V, Pucovský V, Bolton T B
Division of Basic Medical Sciences, Ion Channels and Cell Signalling Centre, St. George's University of London, UK.
Cell Calcium. 2008 Feb;43(2):122-41. doi: 10.1016/j.ceca.2007.04.012. Epub 2007 Jun 13.
Membrane depolarization triggers Ca(2+) release from the sarcoplasmic reticulum (SR) in skeletal muscles via direct interaction between the voltage-gated L-type Ca(2+) channels (the dihydropyridine receptors; VGCCs) and ryanodine receptors (RyRs), while in cardiac muscles Ca(2+) entry through VGCCs triggers RyR-mediated Ca(2+) release via a Ca(2+)-induced Ca(2+) 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 Ca(2+) 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 Ca(2+). The initial abrupt sub-PM Ca(2+) upstroke was all but abolished by block of VGCCs (by 5 microM nicardipine), depletion of intracellular Ca(2+) stores (with 10 microM cyclopiazonic acid) or inhibition of IP(3)Rs (by 2 microM xestospongin C or 30 microM 2-APB), but was not affected by block of RyRs (by 50-100 microM tetracaine or 100 microM 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 Ca(2+) entry through VGCCs which evokes an initial IP(3)R-mediated Ca(2+) release activated via a CICR mechanism.
膜去极化通过电压门控L型钙通道（二氢吡啶受体；VGCCs）与兰尼碱受体（RyRs）之间的直接相互作用，触发骨骼肌肌浆网（SR）释放Ca(2+)。而在心肌中，通过VGCCs的Ca(2+)内流通过钙诱导钙释放（CICR）机制触发RyR介导的Ca(2+)释放。在此我们证明，在豚鼠小肠的相性平滑肌中，毒蕈碱受体激活引起的兴奋触发富含肌醇1,4,5-三磷酸受体（IP(3)Rs）且RyRs较少的亚膜下（sub-PM）SR元件突然释放Ca(2+)。随后[Ca(2+)]i有较小幅度的升高或振荡。初始的亚膜下[Ca(2+)]i突然升高几乎完全被VGCCs阻断（用5 microM尼卡地平）、细胞内钙库耗竭（用10 microM环匹阿尼酸）或IP(3)Rs抑制（用2 microM西司他汀C或30 microM 2-APB）所消除，但不受RyRs阻断（用50 - 100 microM丁卡因或100 microM兰尼碱）的影响。抑制IP(3)Rs或RyRs可使相性毒蕈碱收缩减弱73%。因此，与心肌不同，这种相性内脏平滑肌中的兴奋-收缩偶联是通过VGCCs的Ca(2+)内流发生的，该内流引发经由CICR机制激活的初始IP(3)R介导的Ca(2+)释放。
