Open AccessMechanism by which metabolic inhibitors depolarize cultured cardiac cells.
Author(s) -
William T. Clusin
Publication year - 1983
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.80.12.3865
Subject(s) - depolarization , biophysics , purkinje fibers , pacemaker potential , hyperpolarization (physics) , iodoacetic acid , intracellular , membrane potential , chemistry , repolarization , extracellular , dinitrophenol , cardiac action potential , ouabain , biology , medicine , electrophysiology , biochemistry , sodium , stereochemistry , enzyme , nuclear magnetic resonance spectroscopy , organic chemistry
To elucidate the means by which metabolic inhibition depolarizes cardiac cells, spontaneously beating chicken embryonic myocardial cell aggregates were voltage clamped during superfusion with 2,4-dinitrophenol and iodoacetic acid. In aggregates continuously clamped in the pacemaker potential range, abrupt exposure to these metabolic inhibitors produced a slow transient inward current. This inward current was not due to an alteration of the pacemaker current, IK2, because it could still be elicited after IK2 was abolished by Cs+ ions. The inward current was increased by hyperpolarization and decreased by depolarization. It became larger and more sustained if intermittent action potentials were allowed during exposure or if the aggregates were pretreated with either 10 mM Ca2+ or 2.7 microM acetylstrophanthidin. The inward current was suppressed by removal of extracellular Na+ or Ca2+. These observations suggest that early depolarization of cultured cardiac cells by metabolic inhibitors involves some of the same mechanisms as the transient inward current of digitalis toxicity--specifically, an effect of intracellular Ca2+ ions on membrane permeability. Similar phenomena could occur during other forms of metabolic inhibition such as myocardial ischemia.