Intracellular acidosis modulates the stretch-induced changes in E–C coupling of the rat atrium
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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Document Type: Research Article
Affiliations: University of Oulu, Department of Physiology, Department of Physical Sciences, Division of Biophysics and Biocenter Oulu, Kajaanintie 52 A, Oulu, Finland
Publication date: 01 November 1999