Studies on mercury-induced myotonia in the mouse diaphragm.

Muscle contracture and myotonia of mouse diaphragm, induced by HgCl2, were studied. HgCl2 induced myotonia of mouse diaphragm only on condition that the Hg2+ contracture was inhibited by 0.005-0.01 mM NaCN. A higher concentration of 0.05 mM NaCN abolished both the Hg2+ contracture and Hg2+ myotonia. This finding suggests that the Hg2+ contracture masked the Hg2+ myotonia which was less sensitive to the inhibitory action of NaCN. This differential inhibitory action of NaCN on Hg2+ contracture from Hg2+ myotonia implies a possibility that NaCN antagonized the actions of HgCl2 not only through a simple chemical interaction. Hg2+ myotonia was characterized by an increase in contractile amplitude and a prolongation of contractile duration which were associated with stimulus-bound repetitive action potentials and an increase in membrane input resistance. A low Cl- medium as well as a Cl- channel blocker (9-anthracene carboxylic acid) not only by themselves induced myotonia, but also antagonized Hg2+ myotonia. Thus, Hg2+ appeared to mimic the Cl- channel blocker in inducing myotonia through a blockade of the Cl- channel. K+ channel blockers (4-aminopyridine, uranyl nitrate and tetraethylammonium chloride), as well as low (0.25 mM) Ca2+ Krebs, augmented Hg2+ myotonia while ATP-sensitive K+ channel blockers (tolbutamide and glibenclamide) antagonized Hg2+ myotonia (in the presence of NaCN). Since glibenclamide did not affect myotonia induced by a Cl- channel blocker, it was suggested that glibenclamide inhibited the Hg2+ myotonia through an interaction either directly or indirectly with NaCN on the sarcolemma. All of these findings suggest that K+ channels (delayed rectifier and Ca(2+)-activated K+ channel) functionally cooperated with the Cl- channel of the sarcolemma in the regulation of the skeletal muscle contraction. In this study, K+ channel blockers synergistically cooperated with Cl- channel blockers in inducing myotonia of the mouse diaphragm, while an ATP-sensitive K+ channel blocker exerted only an opposite effect on NaCN. Ca2+ appeared to play an important role in regulating the ionic channel activities, especially the Cl- channel, since low Ca2+ markedly potentiated not only Hg2+ but also low Cl- in inducing myotonia.