Calcineurin trapped in liposomes inhibits the action potentials of isolated 3-days-old embryonic chick ventricle.
Calcineurin, an intracellular protein phosphatase (type 2B), is reported to inhibit L-type (slow) calcium channels and thereby play a key role in channel inactivation. The present study was undertaken to examine effects of calcineurin on slow channel dependent action potentials of 3-days-old embryonic chick ventricle and to assess the role of this enzyme in regulation of developing slow channels. Calcineurin trapped in phosphatidylcholine-liposomes to facilitate its intracellular uptake was found to inhibit maximal upstroke velocity (+Vmax), overshoot and duration of action potentials. At higher doses of calcineurin containing liposomes the preparations ceased to exhibit spontaneous activity but elicited electrically driven action potentials with lower +Vmax and overshoot. These observations show that calcineurin down-modulates the embryonic cardiac slow channels under basal conditions.
Tripathi
O
O
Department of Physiology & Biophysics University of Cincinnati, College of Medicine, Ohio 45267.
Sperelakis
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D019703:Calcineurin; D002147:Calmodulin / Q000008:administration & dosage / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005318:Fetal Heart / Q000187:drug effects*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008081:Liposomes; D010713:Phosphatidylcholines; D010749:Phosphoprotein Phosphatases / Q000008:administration & dosage* / Q000494:pharmacology
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D004338:Drug Combinations; D008081:Liposomes; D010713:Phosphatidylcholines; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases