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  • 标题:Intracellular Na+ modulates the cAMP-dependent regulation of ion channels in the heart.
  • 本地全文:下载
  • 作者:R D Harvey ; J A Jurevicius ; J R Hume
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1991
  • 卷号:88
  • 期号:16
  • 页码:6946-6950
  • DOI:10.1073/pnas.88.16.6946
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The cAMP-dependent regulation of ion channels was studied by using the whole-cell configuration of the patch clamp technique. In isolated cardiac ventricular myocytes, the beta-adrenergically regulated Cl- current (ICl) exhibited an unusual dependence on Na+, such that replacement of extracellular Na+ with compounds such as tetramethylammonium, choline, Tris, or N-methyl-D-glucamine resulted in a reduction in current amplitude without changing the reversal potential. Replacement of extracellular Na+ with tetramethylammonium also reduced the magnitude of the beta-adrenergically enhanced Ca2+ current and delayed rectifier K+ current, suggesting that removal of Na+ was affecting the cAMP pathway that regulates all three currents. Replacement of extracellular Na+ also reduced ICl that was stimulated by (i) direct activation of adenylate cyclase with forskolin, (ii) inhibition of phosphodiesterase with 3-isobutyl-1-methylxanthine, (iii) exposure to the membrane-permeable cAMP derivative 8-bromoadenosine 3',5'-cyclic monophosphate, or (iv) direct phosphorylation of the channel with protein kinase A catalytic subunit. This suggests that the Na+ dependence is at a point beyond the activation of protein kinase A. The Na+ dependence of ICl regulation could not be explained by changes in intracellular Ca2+. However, the sensitivity of the ICl to changes in extracellular Na+ depended significantly on the intracellular Na+ concentration, suggesting that intracellular Na+ plays an important role in the cAMP-dependent regulation of ion channels.
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