Intracellular pH regulation in heart

Intracellular pH (pHi) 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 pHi 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 pHi 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 pHi 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 pHi regulation plays in the heart.