CALCIUM CONTROL ON INSP(3)-INDUCED DISCHARGE OF CALCIUM FROM PERMEABILIZED HEPATOCYTE POOLS
CALCIUM CONTROL ON INSP(3)-INDUCED DISCHARGE OF CALCIUM FROM PERMEABILIZED HEPATOCYTE POOLS
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DOI：
10.1016/0143-4160(93)90049-c
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发表时间：
1993-04-01
期刊：
影响因子：
4
通讯作者：
CHAMPEIL, P
中科院分区：
文献类型：
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作者：
COMBETTES, L;CLARET, M;CHAMPEIL, P
通过在20 ℃下结合Quin-2和Ca 2+测量，研究了腔内和胞浆Ca 2+对InsP 3诱导的皂苷透化大鼠肝细胞悬浮液中胞内Ca 2+池中Ca 2+释放的控制。我们未能检测到管腔内Ca 2+在调节这种释放中的主要作用，因为其中Ca 2+池的负荷以2倍变化的各种操作并不显著影响InsP 3在释放Ca 2+中的表观相对效率;这些操作包括通过在各种外部游离Ca 2+浓度下初步平衡将Ca 2+库加载到各种稳态水平，以及通过阻断泵介导的Ca 2+摄取逐渐排空它们。至于Ca 2+的胞质侧，在最近的结果与其他系统相比，我们发现，在最大剂量，InsP 3诱导的Ca 2+释放不刺激提高Ca 2+从非常低的亚微摩尔或微摩尔浓度，只有相对较高浓度的游离Ca 2+抑制这种释放（半最大抑制是3和15 μ M之间）。这种升高的Ca 2+浓度降低了InsP 3敏感的Ca 2+池的大小。我们还注意到，在pCa 5时InsP 3激活释放的表观协同性明显低于在pCa 7时观察到的协同性。结果，在低InSP 3浓度下，胞质Ca 2+从pCa 7升高至pCa 5刺激InSP 3介导的Ca 2+释放。这些结果进行了讨论的背景下，目前的猜测，组织特异性，异质性，量子释放，振荡，和几种不同的机制，可能控制InsP 3诱导的Ca 2+释放。
The control exerted by intralumenal and cytosolic Ca2+ on InsP3-induced release of Ca2+ from intracellular Ca2+ pools in suspensions of saponin-permeabilised rat hepatocytes was investigated by combined Quin-2 and Ca2+ measurements at 20-degrees-C. We failed to detect a major effect of intralumenal Ca2+ in regulating this release, as various manipulations in which the load of the Ca2+ pools was varied by a factor of two did not significantly affect the apparent relative efficiency of InsP3 in releasing Ca2+; these manipulations included loading the Ca2+ pools up to various steady state levels by preliminary equilibration at various external free Ca2+ concentrations, as well as emptying them progressively through the blockade of pump-mediated Ca2+ uptake. As regards Ca2+ on the cytosolic side, in contrast with recent results obtained with other systems, we found that, at maximal doses, InsP3-induced Ca2+ release was not stimulated by raising Ca2+ from very low to submicromolar or micromolar concentrations, and that only relatively high concentrations of free Ca2+ inhibited this release (half-maximal inhibition was between 3 and 15 muM). Such elevated Ca2+ concentrations reduced the size of the InsP3-sensitive Ca2+ pool. We also noted that the apparent cooperativity of InsP3 activation of release at pCa 5 was noticeably less than that observed at pCa 7. As a result, at low InSP3 concentrations, a rise in cytosolic Ca2+ from pCa 7 to pCa 5 stimulated InSP3-mediated Ca2+ release. These results are discussed in the context of the current speculations about tissue specificity, heterogeneity, quantal release, oscillations, and the several different mechanisms that may control InsP3-induced Ca2+ release.