AUTHOR=van Borren Marcel , Vos Marc , Houtman Marien , Antoons Gudrun , Ravesloot Jan H. TITLE=Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block JOURNAL=Frontiers in Physiology VOLUME=4 YEAR=2013 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2013.00322 DOI=10.3389/fphys.2013.00322 ISSN=1664-042X 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/μm²/min in normal myocytes to 15 ± 2.4 amol/μm²/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.