title: Contraction and intracellular Ca2+, Na+, and H+ during acidosis in rat ventricular myocytes.
abstract: We have investigated the effect of a CO2-induced (respiratory) acidosis on contraction and on intracellular Ca2+, Na+, and pH (measured using the fluorescent dyes fura-2, sodium-binding benzofuran isophthalate, and 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein, respectively) in ventricular myocytes isolated from rat hearts. Initial exposure to acidosis led to a rapid decrease in intracellular pH that was accompanied by an abrupt decline in contractility. There were no consistent changes of intracellular Na+ or Ca2+ during this period. The rapid decline of contractility was followed by a slower partial recovery, which was accompanied by increases in intracellular Na+, systolic and diastolic Ca2+, and an increase in the Ca2+ content of the sarcoplasmic reticulum (estimated using caffeine). Intracellular pH did not change during this slow recovery. The slow rise of intracellular Na+ and the recovery of the twitch were blocked by the Na(+)-H+ exchange inhibitor amiloride. The sarcoplasmic reticulum inhibitor ryanodine blocked the recovery of the twitch but had no effect on the rise of intracellular Na+ induced during acidosis. It is concluded that a major cause of the initial decline of the twitch during acidosis is a decrease in the response of the contractile proteins to Ca2+ due to the decrease of intracellular pH. The subsequent slow recovery of the twitch is due to the decrease of intracellular pH activating the Na(+)-H+ exchange mechanism. This elevates intracellular Na+ and presumably, via the Na(+)-Ca2+ exchange mechanism, intracellular Ca2+. This in turn may lead to increased Ca2+ loading of, and hence release from, the sarcoplasmic reticulum, and it is this that underlies the partial recovery of contraction during acidosis in this preparation.
authors.affiliation: Department of Physiology, University of Leeds, United Kingdom.
authors.forename: S M
authors.initials: SM
authors.lastname: Harrison
authors.forename: J E
authors.initials: JE
authors.lastname: Frampton
authors.forename: E
authors.initials: E
authors.lastname: McCall
authors.forename: M R
authors.initials: MR
authors.lastname: Boyett
authors.forename: C H
authors.initials: CH
authors.lastname: Orchard
mesh_terms: D000138:Acidosis / Q000378:metabolism* / Q000473:pathology; D000142:Acidosis, Respiratory / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006352:Heart Ventricles; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D007477:Ions; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D007477:Ions; D012433:Ryanodine; D000584:Amiloride; D006859:Hydrogen; D012964:Sodium; D002118:Calcium