Acidosis depresses delayed afterdepolarization in guinea pig myocardium.

We examined the relationship among intracellular sodium activity (aiNa), intracellular pH (pHi), and delayed afterdepolarization (DAD) in guinea pig ventricular papillary muscle fibers exposed to K-free solution in vitro, using Na+- and H+-selective microelectrodes. In unstimulated papillary muscles, exposure to K-free solution caused a rapid increase in aiNa of 16.2-22 mM at the end of a 20-min superfusion period with rates of 0.51-0.73 mM/min. This was paralleled by a decrease in intracellular pH of 0.10-0.15 units. DADs were induced after a train of driven action potentials 5-15 min after superfusion with K-free solution at the elevated aiNa from the steady-state level. Prevention of intracellular acidosis associated with the increased aiNa in K-free solution by external alkalosis at pH 8.0 enhanced the amplitude of the DAD, whereas restoration of external pH to 7.4 and a further acidification of external pH to 6.4 suppressed DADs. We concluded that intracellular acidosis associated with the increased aiNa per se increased the likelihood for inhibition of sarcoplasmic reticulum Ca2+ release in spite of increased cytosolic Ca2+.