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.
Fu
W M
WM
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Republic of China.
Day
S Y
SY
Lin-Shiau
S Y
SY
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000503:physiopathology; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009222:Myotonia / Q000139:chemically induced* / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D012132:Respiratory Muscles / Q000187:drug effects* / Q000503:physiopathology
D002712:Chlorides; D015221:Potassium Channels; D002104:Cadmium; D002118:Calcium