By inducing a small reduction of the intracellular pH (0.18 units) with 20 mmol L-1 propionate we demonstrated that acidification changed the responses of isolated rat atria to stretch. Stretch (increase of the intra-atrial pressure) in normal pH increased the Ca2+ transients' amplitude (Indo-1 fluorescence) from 0.26 +- 0.09 in 1 mmHg to 0.36 +- 0.13 in 4 mmHg (P < 0.05, n=6), without affecting the diastolic [Ca2+]i level (n.s. n=6). The changes in Ca2+ balance during stretch were accompanied by a biphasic increase in the contraction force. Five minutes of continuous stretch increased the action potential duration (APD90%, P < 0.01, n=13) and decreased the APD15% (P < 0.001, n=13). During acidosis, the stretch-induced increase of the Ca2+ transient amplitude (0.4 +- 0.13 vs. 0.3 +- 0.08, P < 0.05, n=6) was accompanied by the increase of the diastolic [Ca2+]i (1.16 +- 0.07, P < 0.05, n=6) compared with non-acidotic control (1.06 +- 0.06, n=6). Acidic intracellular pH also inhibited the stretch-induced changes in the action potentials (n=10) and slowed down the development of the contractile force during stretch. The results showed that acidosis modulates the mechanotransduction. It does this by interfering with the intracellular Ca2+ balance, inhibiting the Ca2+ extrusion mechanisms and reducing the Ca2+-buffering power of the cells. The physiological and pathological processes associated with stretch are therefore modulated by intracellular pH owing to its concerted effects on intracellular Ca2+ handling caused by a competitive inhibition of various Ca2+-binding molecules.
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