title: Apamin, a highly potent blocker of the TTX- and Mn2(+)-insensitive fast transient Na+ current in young embryonic heart.
abstract: The whole-cell current clamp and voltage clamp techniques were used to record the slow Na+ action potentials (APs) and the inward current in cultured single ventricular cells isolated from young (3 day-old) embryonic chicks. The slow Na+ APs had a +Vmax of 21.5 +/- 7.5 V/s (in 10 different single cells) and the macroscopic inward current responsible for the rising phase of these APs was a fast transient (ft) current. The ft inward current was sensitive to changes in [Na]o but not to changes in [Ca]o. This channel was found to be permeable to Li+ and Ba2+. Analysis of Na+ current decay suggests a second-order process of current decay. The slow Na+ APs and the ft inward current were insensitive to tetrodotoxin (TTX) and Mn2+. This current was also insensitive to the inorganic Ca2+ blockers, Ni2+, Cd2+ and La3+. At low concentration (10(-9)-10(-6) M) the organic Ca2+ blockers, (-)D888 and nifedipine had no effect on the TTX- and Mn2(+)-insensitive INa. However, at a high concentration (10(-5) M), the Ca2+ blockers, (-)D888 and nifedipine, completely blocked the slow Na+ APs and the TTX- and Mn2(+)-insensitive ft inward Na+ current responsible for the rising phase of the APs. High concentration of verapamil (10(-5) M) and D-600 (10(-5) M) had little depressant effects due to their frequency dependence. Apamin, a toxin in the bee venom, that was previously reported by our group to block the slow Ca2+ APs (Bkaily et al., 1985) and the slow Ca2+ current (Bkaily et al., 1988b), greatly decreased the TTX- and Mn2(+)-insensitive ft INa at 10(-10) M. Thus, the inward current responsible for the rising phase of the slow Na+ APs in 3 day-old embryonic chick heart shows fast transient activation and is TTX- and Mn2(+)-insensitive. This channel is highly sensitive to apamin and shares few characteristics with the Ca2+ channel and the TTX-sensitive fast Na+ channel.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Bkaily
authors.forename: D
authors.initials: D
authors.lastname: Jacques
authors.forename: A
authors.initials: A
authors.lastname: Sculptoreanu
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: D
authors.initials: D
authors.lastname: Carrier
authors.forename: D
authors.initials: D
authors.lastname: Vigneault
authors.forename: N
authors.initials: N
authors.lastname: Sperelakis
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D001464:Barium / Q000493:pharmacokinetics / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002642:Chick Embryo; D004553:Electric Conductivity / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology; D008094:Lithium / Q000493:pharmacokinetics / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism* / Q000493:pharmacokinetics; D013779:Tetrodotoxin / Q000494:pharmacology*; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001030:Apamin; D001464:Barium; D008345:Manganese; D013779:Tetrodotoxin; C043184:4-desmethoxyverapamil; D008094:Lithium; D012964:Sodium; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium