The metabolic inhibitor antimycin A can disrupt cell-to-cell communication by an ATP- and Ca2+-independent mechanism

被引:9
作者
Plaisance, I
Duthe, F
Sarrouilhe, D
Hervé, JC
机构
[1] Univ Poitiers, Fac Sci Fondamentales & Appl, CNRS, UMR Commun Jonct 6558, F-86022 Poitiers, France
[2] Univ Poitiers, Fac Med Pharm, Lab Physiol Humaine, F-86005 Poitiers, France
来源
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY | 2003年 / 447卷 / 02期
关键词
cytoplasmic continuity; gap junction; metabolic inhibition; patch clamp; protein kinases;
D O I
10.1007/s00424-003-1158-0
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
In cardiac myocytes of new-born rats, the degree of intercellular communication through gap junctional channels closely depends on the metabolic state of the cells. In contrast, in stably transfected HeLa cells expressing rat cardiac connexin43 (Cx43, the main channel-forming protein present in ventricular myocytes), a major part of junctional communication persisted in ATP-depleted conditions, in the presence of a metabolic inhibitor (KCN) or of a broad spectrum inhibitor of protein kinases (H7). However, another metabolic inhibitor, antimycin A, which like cyanide inhibits electron transfer in the respiratory chain, totally interrupted cell-to-cell communication between Cx43-HeLa cells, even in whole-cell conditions, when ATP (5 mM) was present. Antimycin A caused a modest increase in cytosolic calcium concentration; however, junctional uncoupling still occurred when this rise was prevented. Conditions of ischemic insult (e.g. ischemia or chemical hypoxia) frequently cause the activation of protein kinases, particularly of Src and MAP kinases, and such activations are known to markedly disrupt gap junctional communication. Antimycin-induced junctional uncoupling occurred even in the presence of inhibitors of these kinases. Antimycin A appears able to cause junctional uncoupling either through the ATP depletion it induces as a metabolic poison or via a direct action on gap junction constituents.
引用
收藏
页码:181 / 194
页数:14
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