Persistent sodium currents induced by anthopleurin-A and their relationship to early afterdepolarizations in ventricular myocytes.
Prolonged Na+ current inactivation was induced in neonatal rat ventricular myocytes by exposure to Anthopleurin-A (80-240 nM). In control whole-cell voltage clamp recordings, prolonged Na+ current inactivated mono-exponentially from peak with time constant, tau h, averaging 1.5 msec +/- 0.2 msec at -30 mV and peak current averaging 0.7 +/- 0.3 nA (n = 10). Steady state inactivation was complete at -50 mV and there was little or no overlap of prolonged Na+ current inactivation and activation processes. One to 3 minutes following exposure to Anthopleurin-A, the rate of inactivation slowed, with tau h increasing to 21 +/- 5 msec at -30 mV, and peak prolonged Na+ current increasing to 1.3 +/- 0.5 nA (n = 10). Steady state inactivation was shifted in a positive direction, and complete inactivation did not occur even at +10 mV. Persistent inward currents were thus induced by Anthopleurin-A. They were most prominent at depolarizations slightly above threshold for activation and were selectively blocked by lidocaine (60 microM). Action potentials were prolonged by Anthopleurin-A, especially at slow stimulation rates, and were accompanied by early afterdepolarizations. The correlation between persistent inward currents and early afterdepolarizations, in terms of voltage dependence, appearance and pharmacology, suggests a possible causal role for persistent Na+ currents in this model of early afterdepolarizations.
Craelius
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W
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08855.
Green
W
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Wu
K M
KM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D012615:Sea Anemones; D012964:Sodium / Q000502:physiology*
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C012746:anthopleurin-A; D012964:Sodium