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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jurevicius, J. A. Hume, J. R. Harvey, R. D. |
| Description | Author Affiliation: Harvey RD ( Department of Physiology, University of Nevada School of Medicine, Reno 89557.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 88 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1991-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | 8-Bromo Cyclic Adenosine Monophosphate Pharmacology Calcium Channels Physiology Cyclic AMP Heart Ion Channels Membrane Proteins Sodium 1-Methyl-3-isobutylxanthine Animals Drug Effects Cells, Cultured Chloride Channels Colforsin Guinea Pigs Heart Ventricles Homeostasis Isoproterenol Kinetics Membrane Potentials Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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