Mode of stimulatory actions of cadmium ion on the mouse diaphragm

Effects of Cd2+ on the phrenic nerve-diaphragm preparation of the mouse varied markedly in media containing various Ca2+ concentrations. In normal 2.5 mM Ca2+ medium, Cd2+ inhibited acetylcholine release from nerve endings without appreciable effect on the muscle membrane. However, Cd2+ elicited stimulatory effects on the muscle membrane in low Ca2+ medium (10(-3)-1 mM). These stimulatory effects included the induction of spontaneous contractions, augmentation of twitch responses to direct electrical stimulation and potentiation of the muscle contracture induced by acetylcholine, carbachol and high K+. By contrast, caffeine contracture was not affected by Cd2+. Tetrodotoxin, procaine, cysteine and glycerol pretreatment abolished these stimulatory effects of Cd2+. Moreover, changing the ionic composition of the bathing medium to one containing low Na+, high K+, high Mg2+ or high Ca2+ also antagonized these effects of Cd2+. In contrast, low Mg2+ markedly potentiated the frequency of spontaneous contractions induced by Cd2+. (+)-Tubocurarine and beta-bungarotoxin had no effect on Cd2+-induced spontaneous contractions indicating that they may be myogenic rather than neurogenic in origin. By use of conventional microelectrodes, it was found that Cd2+ not only depolarized the muscle membrane but also induced spontaneous action potentials at a high frequency (173 +/- 17 Hz). It is concluded that increased Na+ permeability of the muscle membrane is the essential step bringing about spontaneous contractions. The binding of Cd2+ to -SH groups of the membrane is closely related to the induction of these effects.