title: Increased sarcolemmal Na(+)/H(+) exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block.
abstract: 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.
authors: Heart Failure Research Center, Academic Medical Center, University of Amsterdam Netherlands.
authors: Marcel M G J
authors: MM
authors: van Borren
authors: Marc A
authors: MA
authors: Vos
authors: Marien J C
authors: MJ
authors: Houtman
authors: Gudrun
authors: G
authors: Antoons
authors: Jan H
authors: JH
authors: Ravesloot
keywords: AE; CHE; NBC; NHE-1; compensated cardiac hypertrophy