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J Am Coll Cardiol, 2000; 36:534-540
© 2000 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Sarcolemmal Na+/H+ exchanger activity and expression in human ventricular myocardium

Hiroyuki Yokoyama, MDa, Suba Gunasegaram, BSca, Sian E. Harding, PhD* and Metin Avkiran, PhDa

a Center for Cardiovascular Biology and Medicine, King’s College London, London, United Kingdom
* National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom

Manuscript received September 30, 1999; revised manuscript received January 20, 2000, accepted March 29, 2000.

Reprint requests and correspondence to: Dr. Metin Avkiran, Cardiovascular Research, The Rayne Institute, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom
metin.avkiran{at}kcl.ac.uk

OBJECTIVES

To determine sarcolemmal Na+/H+ exchanger (NHE) activity and expression in human ventricular myocardium.

BACKGROUND

Although the sarcolemmal NHE has been implicated in various physiological and pathophysiological phenomena in animal studies, its activity and expression in human myocardium have not been studied.

METHODS

Ventricular myocardium was obtained from unused donor hearts with acute myocardial dysfunction (n = 5) and recipient hearts with chronic end stage heart failure (n = 11) through a transplantation program. Intracellular pH (pHi) was monitored in enzymatically isolated single ventricular myocytes by microepifluorescence. As the index of sarcolemmal NHE activity, the rate of H+ efflux at a pHi of 6.90 (JH6.9) was determined after the induction of intracellular acidosis in bicarbonate-free medium. Na+/H+ exchanger isoform 1 (NHE1) expression in ventricular myocardium was determined by immunoblot analysis.

RESULTS

Human ventricular myocytes exhibited readily detectable sarcolemmal NHE activity after the induction of intracellular acidosis, and this activity was suppressed by the NHE1-selective inhibitor HOE-642 (cariporide) at 1 µmol/L. Sarcolemmal NHE activity of myocytes was significantly greater in recipient hearts (JH6.9 = 1.95 ± 0.18 mmol/L/min) than it was in unused donor hearts (JH6.9 = 1.06 ± 0.15 mmol/L/min). In contrast, NHE1 protein was expressed in similar abundance in ventricular myocardium from both recipient and unused donor hearts.

CONCLUSIONS

Sarcolemmal NHE activity of human ventricular myocytes arises from the NHE1 isoform and is inhibited by HOE-642. Sarcolemmal NHE activity is significantly greater in recipient hearts with chronic end-stage heart failure than it is in unused donor hearts, and this difference is likely to arise from altered posttranslational regulation.

Abbreviations and Acronyms
  betai = intrinsic buffering power
  dpHi/dt = rate of recovery of pHi
  JH = rate of H+ efflux
  JH6.9 = rate of H+ efflux at pHi 6.90
  NCE = Na+/Ca2+ exchanger
  NHE = Na+/H+ exchanger
  NHE1 = Na+/H+ exchanger isoform 1
  pHi = intracellular pH




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