The myotonic mouse mutant ADR: electrophysiology of the muscle fiber

Abstract

The hereditary neuromuscular syndrome of the mouse, "arrested development of righting response" (ADR), is characterized by after-contractions of skeletal muscle. In order to analyze the etiology of this hereditary defect, mutant and wildtype muscle fibers were studied by intracellular recording. Direct stimulation of ADR muscle fibers elicited runs of action potentials of 1-5 seconds duration, with declining amplitudes and varying frequencies. The electrical after-activity coincided with after-contractions of the fiber, and both phenomena could be suppressed by the membrane-stabilizing drug tocainide. Since similar runs of APs were observed with wildtype muscle in chloride-free medium, the possible involvement of chloride conductance in the ADR syndrome was studied. Although membrane time constants in wildtype muscle were 4 times prolonged in chloride-free medium, those of ADR muscle were only 1.4 times longer. This finding indicated a drastic reduction of chloride conductance of the ADR muscle membrane. We conclude that ADR is a myotonia, related in its etiology to hereditary myotonias of man.