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Circulation Research. 1996;78:707-716

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*Compound via MeSH
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*4,4'-DINITRO-2,2'-STILBENEDISULFONIC ACID
*CALCIUM COMPOUNDS
*CALCIUM, ELEMENTAL
(Circulation Research. 1996;78:707-716.)
© 1996 American Heart Association, Inc.


Articles

Ca2+-Induced Current Oscillations in Rabbit Ventricular Myocytes

Michael A. Laflamme, Peter L. Becker

From the Department of Physiology, Emory University School of Medicine, Atlanta, Ga.

Correspondence to Dr Peter L. Becker, Department of Physiology, Emory University School of Medicine, 1648 Pierce Dr, Atlanta, GA 30322. E-mail plb@physio.emory.edu.

Abstract Transient currents are activated by spontaneous Ca2+ oscillations in rabbit ventricular myocytes. We investigated the ionic basis for these transient currents under conditions in which K+ currents would be expected to be blocked. Holding cells under voltage clamp at positive potentials leads to a rise in intracellular Ca2+ via reversal of the Na+-Ca2+ exchanger and subsequently to the initiation of spontaneous Ca2+ transients, presumably from a Ca2+-overloaded sarcoplasmic reticulum. The current transients associated with these Ca2+ transients reversed at about +10 to +15 mV under conditions of approximately symmetrical Cl-. In the absence of Cl-, this current was inward at all potentials examined over the range from -88 to +72 mV, consistent with a Na+-Ca2+ exchanger current. In the absence of Na+, the repetitive spontaneous Ca2+ transients could be initiated by a brief train of depolarizations to activate the inward Ca2+ current. Under such conditions, the current was found to reverse at -3 mV when the equilibrium potential of Cl- (ECl) was -2 mV, and the reversal potential shifted to -32 mV when internal Cl- was lowered, to make ECl -33 mV. Thus, in the absence of Na+, it appears that the current is exclusively a Ca2+-activated Cl- current. There is no evidence to indicate the presence of a Ca2+-activated cationic conductance. Further, our results demonstrate that the Ca2+-activated Cl- conductance can carry inward current at potentials more negative to ECl in rabbit ventricular myocytes and is therefore likely to contribute to the arrhythmogenic delayed afterdepolarizations that occur in Ca2+-overloaded cells.


Key Words: Cl- current • Ca2+ oscillations • transient inward current • Na+-Ca2+ exchanger • rabbit ventricular myocytes




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