Studies on cadmium-induced myotonia in the mouse diaphragm

Summary

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 [CI⁻]_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.