Intracellular pH regulation in heart

Abstract 

Intracellular pH (pH_i) is an important modulator of cardiac excitation and contraction, and a potent trigger of electrical arrhythmia. This review outlines the intracellular and membrane mechanisms that control pH_i in the cardiac myocyte. We consider the kinetic regulation of sarcolemmal H⁺, OH⁻ and HCO₃⁻ transporters by pH, and by receptor-coupled intracellular signalling systems. We also consider how activity of these pH_i effector proteins is coordinated spatially in the myocardium by intracellular mobile buffer shuttles, gap junctional channels and carbonic anhydrase enzymes. Finally, we review the impact of pH_i regulatory proteins on intracellular Ca²⁺ signalling, and their participation in clinical disorders such as myocardial ischaemia, maladaptive hypertrophy and heart failure. Such multiple effects emphasise the fundamental role that pH_i regulation plays in the heart.

Keywords: Cardiac, Heart, Myocyte, pH_i, NHE, NBC, CHE, CBE, H⁺, OH^-, HCO₃^–, Arrhythmia, Contraction, Cardioprotection