Increased sarcolemmal Na(+)/H(+) exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block
Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na(+) influx in hypertrophied cAVB ventricular myocytes contrib...
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Published in | Frontiers in physiology Vol. 4; p. 322 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
01.01.2013
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Subjects | |
Online Access | Get full text |
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Summary: | Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na(+) influx in hypertrophied cAVB ventricular myocytes contribute to these lethal arrhythmias. The increased Na(+) influx was not mediated by Na(+) channels, in fact the Na(+) current proved reduced in cAVB myocytes. Here we tested the hypothesis that increased activity of the Na(+)/H(+) exchanger type 1 (NHE-1), commonly observed in hypertrophic hearts, causes the elevated Na(+) influx. Cardiac acid-base transport was studied with a pH-sensitive fluorescent dye in ventricular myocytes isolated from control and hypertrophied cAVB hearts; the H(+) equivalent flux through NHE-1, Na(+)-HCO(-) 3 cotransport (NBC), Cl(-)/OH(-) exchange (CHE), and Cl(-)/HCO(-) 3 exchange (AE) were determined and normalized per liter cell water and corrected for surface-to-volume ratio. In cAVB, sarcolemmal NHE-1 flux was increased by 65 ± 6.3% in the pH i interval 6.3-7.2 and NBC, AE, and CHE fluxes remained unchanged. Accordingly, at steady-state intracellular pH the total sarcolemmal Na(+) influx by NHE-1 + NBC increased from 8.5 ± 1.5 amol/μm(2)/min in normal myocytes to 15 ± 2.4 amol/μm(2)/min in hypertrophied cAVB myocytes. We conclude that compensated cardiac hypertrophy in cAVB dogs is accompanied with an increased sarcolemmal NHE-1 activity. This in conjunction with unchanged activity of the other acid-base transporters will raise the intracellular Na(+) in hypertrophied cAVB myocytes. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Mark O. Bevensee, University of Alabama at Birmingham, USA This article was submitted to Membrane Physiology and Membrane Biophysics, a section of the journal Frontiers in Physiology. Reviewed by: Ignacio Gimenez, Aragon's Health Sciences Institute, Spain; John Cuppoletti, University of Cincinnati, USA |
ISSN: | 1664-042X 1664-042X |
DOI: | 10.3389/fphys.2013.00322 |