title: Changes in contraction, cytosolic Ca2+ and pH during metabolic inhibition and upon restoration of mitochondrial respiration in rat ventricular myocytes.
abstract: Exposure of cardiac muscle to metabolic poisons reduces the availability of cellular ATP and cardiac dysfunction ensues. In this study rat ventricular myocytes were exposed to 2-deoxyglucose, iodoacetate and cyanide to induce complete metabolic blockade. Changes in contraction, cytosolic Ca2+ and pH were determined during metabolic blockade and following restoration of mitochondrial ATP production. Metabolic blockade resulted in a rapid failure of contractions and Ca2+ transients, a rise of diastolic Ca2+, a cytosolic acidosis and ultimately a rigor contracture. Washing out cyanide during the development of the rigor contracture led to a rapid relaxation of the contracture, a fall in cytosolic Ca2+ and a rapid, partial reversal of the cytosolic acidosis. The partial reversal of the cytosolic acidosis and fall of cytosolic Ca2+ were abolished in the presence of oligomycin. This suggests that the rapid partial recovery of cytosolic acidosis could result from the rephosphorylation of ADP to ATP by the mitochondrial F1,F0-ATPase (a reaction that consumes protons).
authors.affiliation: Department of Physiology, University of Leeds, UK.
authors.forename: M K
authors.initials: MK
authors.lastname: Lancaster
authors.forename: S M
authors.initials: SM
authors.lastname: Harrison
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D012966:Sodium Cyanide / Q000494:pharmacology; D016276:Ventricular Function / Q000502:physiology*
chemical_list: D000963:Antimetabolites; D004791:Enzyme Inhibitors; D007461:Iodoacetates; D009840:Oligomycins; D003847:Deoxyglucose; D012966:Sodium Cyanide; D002118:Calcium; D019807:Iodoacetic Acid