Related Experiment Videos
Early afterdepolarizations produced by d,l-sotalol and clofilium
E Patterson1, B J Scherlag, R Lazzara
1Department of Pharmacology, College of Medicine, University of Oklahoma Health, Sciences Center, Oklahoma City, USA.
Introduction:
The roles for L-type calcium current and Na-Ca exchange in early afterdepolarizations (EADs) attending d,l-sotalol and clofilium were examined in canine Purkinje fibers and in enzymatically dispersed myocytes from canine subepicardium.
Methods And Results:
Spontaneous EADs were compared to EAD formation potentiated by stimulation of Na-Ca exchange and facilitation of ICa-L (Bay K8644). Bay K8644 (10(-8) M) and stimulation of Na-Ca exchange potentiated bradycardia-dependent EADs. Stimulation of Na-Ca exchange in Purkinje fibers pretreated with d,l-sotalol (10(-5) M) and clofilium (10(-7) M) induced EADs at takeoff potentials negative (-63 +/- 4 and -62 +/- 4 mV, respectively) to EADs potentiated by Bay K8644 (10(-8) M) (-33 +/- 2 and -34 +/- 2 mV, respectively, P < 0.05), or EADs induced by Bay K8644 alone (10(-6) M) (-31 +/- 5 mV). In myocytes, Bay K8644 (10(-8) M) potentiated EADs in d,l-sotalol- (10(-6) to 10(-4) M) or clofilium-treated (10(-9) to 10(-7) M) cells at reduced potentials (-10 +/- 3 and -10 +/- 4 mV, respectively) compared to EADs elicited by clofilium or d,l-sotalol alone (-25 +/- 3 and -24 +/- 3 mV, respectively), or stimulation of Na-Ca exchange in the presence of d,l-sotalol or clofilium (-26 +/- 4 and -26 +/- 4 mV, respectively). Spontaneous EADs or EADs elicited by stimulation of Na-Ca exchange coincident with drug treatment were suppressed by increasing Ca02+ but were not suppressed by nifedipine (10(-7) M).
Conclusion:
EADs elicited by d,l-sotalol and clofilium in canine Purkinje tissue and epicardial myocytes are dependent upon Na-Ca exchange rather than ICa-L "window current."