title: Ca2+-dependent slow action potentials in normal and dystrophic mouse skeletal muscle.
abstract: Slowly rising action potentials (APs), previously described in amphibian skeletal muscle, were examined in skeletal muscle of normal and dystrophic mice (129/ReJ strain). A standard two-microelectrode recording technique was used. Muscles were bathed in a solution that was Cl- free (methanesulfonate substituted), high in K+ (20 mM), and contained 15 mM tetraethylammonium. The slow APs were elicited under conditions in which the fast Na+ channels were voltage inactivated (by partial depolarization) and in which the external Na+ concentration was only 10 mM. Increases in external Ca2+ concentration produced increases in slow AP amplitude and duration. Mn2+ (4 mM), La3+ (4 mM), and detubulation with osmotic shock blocked the slow APs. When slow APs were generated at 30-s intervals, their amplitude stayed constant. When they were generated at 15-s intervals, their amplitude decreased progressively and then fell to zero by the 11th stimulus. The Ca antagonists verapamil (10(-5) M) and bepridil (10(-5) M) caused this decrease in amplitude to occur more quickly. Voltage inactivation of the slow APs occurred between -45 and -10 mV. Slow APs recorded from dystrophic muscle fibers were decreased in amplitude and duration compared with those in normal fibers, and there was a reduced incidence of occurrence; 96% of the fibers in normal muscle exhibited slow APs compared with only 46% of dystrophic muscle fibers. In summary, slow Ca2+ APs in mammalian muscle are similar to those in cardiac and amphibian skeletal muscle, and these slow APs are depressed in dystrophic skeletal muscle.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015764:Bepridil; D002118:Calcium / Q000494:pharmacology*; D005990:Glycerol / Q000494:pharmacology; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D009132:Muscles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D011759:Pyrrolidines / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D011759:Pyrrolidines; D014475:Uncoupling Agents; D008345:Manganese; D007811:Lanthanum; D015764:Bepridil; D014700:Verapamil; D005990:Glycerol; D002118:Calcium