ATP counteracts the rundown of gap junctional channels of rat ventricular myocytes by promoting protein phosphorylation

被引:39
作者
Verrecchia, F
Duthe, F
Duval, S
Duchatelle, I
Sarrouilhe, D
Hervé, JC
机构
[1] Univ Poitiers, CNRS, UMR 6558, Lab Physiol Cellulaire, F-86022 Poitiers, France
[2] Univ Poitiers, CNRS, ESA 6031, IBMIG, F-86022 Poitiers, France
[3] Univ Caen, Neurosci Lab, F-14074 Caen, France
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1999年 / 516卷 / 02期
关键词
D O I
10.1111/j.1469-7793.1999.0447v.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. The degree of cell-to-cell coupling between ventricular myocytes of neonatal rats appeared well preserved when studied in the perforated version of the patch clamp technique or, in double whole-cell conditions, when ATP was present in the patch pipette solution. In contrast, when ATP was omitted, the amplitude of junctional current rapidly declined (rundown). 2. To examine the mechanism(s) of ATP action, an 'internal perfusion technique' was adapted to dual patch clamp conditions, and reintroduction of ATP partially reversed the rundown of junctional channels. 3. Cell-to-cell communication was not preserved by a non-hydrolysable ATP analogue (5'-adenylimidodiphosphate, AMP-PNP), indicating that the effect most probably did not involve direct interaction of ATP with the channel-forming proteins. 4. An ATP analogue supporting protein phosphorylation but not active transport processes (adenosine 5'-O-(3-thiotriphosphate), ATP gamma S) maintained normal intercellular communication, suggesting that the effect was due to kinase activity rather than to altered intracellular Ca2+. 5. A broad spectrum inhibitor of endogenous serine/threonine protein kinases (H7) reversibly reduced the intercellular coupling. A non-specific exogenous protein phosphatase (alkaline phosphatase) mimicked the effects of ATP deprivation. The non-specific inhibition of endogenous protein phosphatases resulted in the preservation of substantial cell-to-cell communication in ATP-free conditions. 6. The activity of gap junctional channels appears to require both the presence of ATP and protein kinase activity to counteract the tonic activity of endogenous phosphatase(s).
引用
收藏
页码:447 / 459
页数:13
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