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Intracellular Na+ modulates the cAMP-dependent regulation of ion channels in the heart / R.D Harvey, J.A Jurevicius, J. R. Hume
Type of publication
Straipsnis Web of Science duomenų bazėje / Article in Web of Science database (S1a)
Author(s)
Harvey, RD | University of Nevada School of Medicine, Reno, USA |
Universite Paris-Sud, Faculte de Pharmacie, France | |
Hume, JR | Universite Paris-Sud, Faculte de Pharmacie, France |
Title
Intracellular Na+ modulates the cAMP-dependent regulation of ion channels in the heart / R.D Harvey, J.A Jurevicius, J. R. Hume
Date Issued
1991-08-01
Extent
p. 6946-6950.
Is part of
Proceedings of the National Academy of Sciences of the United States of America. , 1991, vol. 88, no. 16.
Version
Originalus / Original
Field of Science
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 (I(Cl)) 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 I(Cl) 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 I(Cl) regulation could not be explained by changes in intracellular Ca2+. However, the sensitivity of the I(Cl) 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.
Is Referenced by
Type of document
type::text::journal::journal article
ISSN (of the container)
0027-8424
WOS
A1991GB70100010
Other Identifier(s)
(LSMU ALMA)990000025970107106
Coverage Spatial
Jungtinė Karalystė / United Kingdom of Great Britain and Northern Ireland (GB)
Language
Anglų / English (en)