Studies on cadmium-induced myotonia in the mouse diaphragm.

The purpose of this investigation was to study the possible mechanism of the potentiation of the contractile response and myotonia caused by Cd2+ in the mouse diaphragm. Cd2+ increased both amplitude and duration of the contractile response to direct stimulation in either 0.25 mM Ca2+ Krebs or 2.5 mM Ca2+ Krebs containing the K+-channel blockers, 4-aminopyridine, uranyl nitrate or tetraethylammonium ion. High K+ and tetrodotoxin inhibited these effects of Cd2+. Electrophysiological studies revealed that only one or two action potentials were triggered by passing a short depolarizing current across the muscle fibre membrane in 0.25 mM Ca2+ Krebs, but in the presence of Cd2+, a train of action potentials (153 +/- 21 Hz) which lasted for 0.7 +/- 0.2 s was induced. Furthermore, Cd2+ triggered a train of action potentials evoked by a single extracellular direct stimulation on the muscle fibre in 2.5 mM Ca2+ Krebs solution containing either 4-aminopyridine or uranyl nitrate. The membrane depolarized during the repetitive firing and then repolarized immediately after the cessation of repetitive firing. Cd2+ (0.1 mM) increased the input resistance of the muscle fibre by 53 +/- 7% and this effect was inhibited in low [Cl-]o. These findings suggest that the contractile potentiation and myotonia induced by Cd2+ in the mouse diaphragm are mediated by lowering the Cl- conductance of the membrane.