肌浆网和肌膜共同在结肠平滑肌中形成一个被动性钙陷阱。

The sarcoplasmic reticulum and sarcolemma together form a passive Ca2+ trap in colonic smooth muscle.

作者信息

Bradley Karen N, Craig John W, Muir Thomas C, McCarron John G

机构信息

Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, UK.

出版信息

Cell Calcium. 2004 Jul;36(1):29-41. doi: 10.1016/j.ceca.2003.11.008.

DOI:10.1016/j.ceca.2003.11.008

PMID:15126054

Abstract

In smooth muscle, active Ca(2+) uptake into regions of sarcoplasmic reticulum (SR) which are closely apposed to the sarcolemma has been proposed to substantially limit the increase in the cytoplasmic Ca(2+) concentration (Ca(2+)) following Ca(2+) influx, i.e. the 'superficial buffer barrier hypothesis'. The present study has re-examined this proposal. The results suggest that the SR close to the sarcolemma acts as a passive barrier to Ca(2+) influx limiting Ca(2+) changes; for this, SR Ca(2+) pump activity is not required. In single voltage-clamped colonic myocytes, sustained opening of the ryanodine receptor (RyR) (and depletion of the SR) using ryanodine increased the amplitude of depolarisation-evoked Ca(2+) transients and accelerated the rate of Ca(2+) decline following depolarisation. These results could be explained by a reduction in the Ca(2+) buffer power of the cytosol taking place when RyR are opened (i.e. the SR is 'leaky'). Indeed, determination of the Ca(2+) buffer power confirmed it was reduced by approximately 40%. Inhibition of the SR Ca(2+) pump (with thapsigargin) also depleted the SR of Ca(2+) but did not reduce the Ca(2+) buffer power or increase depolarisation-evoked Ca(2+) transients and slowed (rather than accelerated) Ca(2+) removal. However, thapsigargin prevented the ryanodine-induced increase in Ca(2+) decline following depolarisation. Together, these results suggest that when the SR was rendered 'leaky' (a) more of the Ca(2+) entering the cell reached the bulk cytoplasm and (b) Ca(2+) was removed more quickly at the end of cell activation. Under physiological circumstances in the absence of blocking drugs, it is proposed that the SR limits the Ca(2+) increase following influx without the need for active Ca(2+) uptake. The SR and sarcolemma may form a passive physical barrier to Ca(2+) influx, a Ca(2+) trap, which limits the Ca(2+) rise occurring during depolarisation by about 50% and from which the ion only slowly escapes into the main part of the cytoplasm.

摘要

在平滑肌中，有人提出，肌浆网（SR）中与肌膜紧密相邻的区域对钙离子（Ca(2+)）的主动摄取，在很大程度上限制了Ca(2+)内流后细胞质中Ca(2+)浓度（Ca(2+)）的升高，即“表面缓冲屏障假说”。本研究重新审视了这一观点。结果表明，靠近肌膜的SR作为Ca(2+)内流的被动屏障，限制了Ca(2+)的变化；为此，不需要SR的Ca(2+)泵活性。在单个电压钳制的结肠肌细胞中，使用ryanodine持续开放兰尼碱受体（RyR）（以及耗尽SR）会增加去极化诱发的Ca(2+)瞬变的幅度，并加速去极化后Ca(2+)的下降速率。这些结果可以通过RyR开放时（即SR“渗漏”时）细胞质中Ca(2+)缓冲能力的降低来解释。事实上，Ca(2+)缓冲能力的测定证实其降低了约40%。抑制SR的Ca(2+)泵（用毒胡萝卜素）也会耗尽SR中的Ca(2+)，但不会降低Ca(2+)缓冲能力，也不会增加去极化诱发的Ca(2+)瞬变，反而会减缓（而不是加速）Ca(2+)的清除。然而，毒胡萝卜素阻止了ryanodine诱导的去极化后Ca(2+)下降的增加。总之，这些结果表明，当SR变得“渗漏”时，（a）更多进入细胞的Ca(++)到达大量细胞质，（b）在细胞激活结束时Ca(2+)被更快地清除。在没有阻断药物的生理情况下，有人提出，SR限制了内流后Ca(2+)的增加，而不需要主动摄取Ca(2+)。SR和肌膜可能形成一个对Ca(2+)内流的被动物理屏障，一个Ca(2+)陷阱，它将去极化期间发生的Ca(2+)升高限制约50%，并且离子仅缓慢地逸出到细胞质的主要部分。