Myocardial metabolic inhibition and membrane potential, contraction, and potassium uptake.
Interruption of synthesis of ATP during hypoxia or ischemia can produce membrane depolarization that may be related to inhibition of Na+-K+-ATPase. To examine this hypothesis, the effects of exposure of cultured chick embryo ventricular cells to 1 mM cyanide (CN), to 20 mM 2-deoxy-D-glucose (2-DG), to CN + 2-DG, and to ouabain (10(-3) M) on contraction, membrane potential, and 42K uptake were determined. CN produced moderate membrane depolarization and electromechanical uncoupling within 2 min. 2-DG caused marked membrane depolarization with a transient negative inotropic effect. Exposure to CN + 2-DG produced marked depolarization (-38 mV) and mechanical arrest of the cells in a relaxed state. Ouabain produced marked depolarization (-39 mV) and contracture of the cells. Uptake of 42K was inhibited by 10(-3) M ouabain within seconds. However, CN + 2-DG produced no inhibition of 42K uptake within the first 2 min of exposure, and inhibition of the Na pump by CN + 2-DG required 30 min to develop fully. Exposure to CN alone produced no inhibition of 42K uptake, whereas moderate inhibition was produced by 2-DG alone even when substrate for oxidative phosphorylation was provided. We conclude that the acute effects of inhibition of glycolysis and oxidative phosphorylation on membrane potential and contraction in these cells are not due to inhibition of the Na pump and that during partial metabolic inhibition active univalent cation transport in these cells is relatively dependent on ATP derived from glycolysis, whereas contraction is more dependent on ATP supplied by oxidative phosphorylation.
D000818:Animals; D002642:Chick Embryo; D003486:Cyanides / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D003486:Cyanides; D010042:Ouabain; D003847:Deoxyglucose; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium