Role of L-type calcium channel window current in generating current-induced early afterdepolarizations.
BACKGROUND
Early afterdepolarizations (EADs) can give rise to triggered activity and thereby produce cardiac arrhythmias. We used the whole-cell patch clamp technique to examine the relationship between L-type Ca2+ channel window current and the generation of EADs in single ventricular myocytes isolated from guinea pig hearts.


RESULTS
With a high concentration of EGTA in the internal solution and Na(+)-containing physiologic external solution, EADs were induced in unclamped cells by injecting intracellular depolarizing current pulses. During voltage clamp protocols designed to simulate action potentials interrupted by EADs, we recorded an inward shift in total current up to 0.7 pA/pF over 400 msec at test steps in the range of the take-off potential for EADs. Cd2+ (0.2 mM) blocked most of the inward shift of current during the test steps and abolished EADs. When the same voltage clamp protocol was used following perfusion with an Na(+)-free, K(+)-free external solution, the Cd(2+)-sensitive inward currents recorded during the test steps were similar to those obtained in physiologic external solution. The overlapping range of potentials for partial activation of the d and f variables of L-type Ca2+ current ("window" region) measured in Na(+)-free, K(+)-free external solution was virtually the same as the voltage range of the Cd(2+)-sensitive inward currents.


CONCLUSIONS
Our experiments suggest that: (1) EADs can arise under conditions of high EGTA buffering of intracellular [Ca2+]; and (2) under these conditions, L-type Ca2+ channel window current plays a major role in the initiation of EADs.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
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Ming
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Nordin
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Aronson
D000200:Action Potentials; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002469:Cell Separation; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D006168:Guinea Pigs; D006352:Heart Ventricles; D009206:Myocardium / Q000166:cytology; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology
D015220:Calcium Channels; D002104:Cadmium; D004533:Egtazic Acid; D012964:Sodium; D011188:Potassium