Ca2+-dependent slow action potentials in normal and dystrophic mouse skeletal muscle.
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.
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
D011759:Pyrrolidines; D014475:Uncoupling Agents; D008345:Manganese; D007811:Lanthanum; D015764:Bepridil; D014700:Verapamil; D005990:Glycerol; D002118:Calcium