AJP - Heart and Circulatory Physiology, Vol 257, Issue 3 996-1004, Copyright © 1989 by American Physiological Society
Acidosis depresses delayed afterdepolarization in guinea pig myocardium
T. Yano, N. Hotokebuchi, T. Morioka and K. Nishi
Department of Pharmacology, Kumamoto University Medical School, Japan.
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+.
