title: Intracellular acidosis modulates the stretch-induced changes in E-C coupling of the rat atrium.
abstract: 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.
authors.affiliation: University of Oulu, Department of Physiology, Department of Physical Sciences, Division of Biophysics and Biocenter Oulu, Kajaanintie 52 A, Oulu, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Tavi
authors.forename: C
authors.initials: C
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Weckström
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016275:Atrial Function; D016279:Atrial Function, Left / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015220:Calcium Channels; D007476:Ionophores; D011422:Propionates; C029658:propionic acid; D002118:Calcium