Muscle contracture and twitch depression induced by arsenite in the mouse phrenic nerve-diaphragm.
The purpose of this investigation was to explore the possible mechanism of muscle contracture and twitch depression induced by arsenite in the mouse diaphragm. Arsenite-contracture was dependent on extracellular Ca2+; both EGTA and Ca(2+)-channel blockers (nifedipine and verapamil) inhibited arsenite-contracture. However, the activators caffeine and ryanodine and the inhibitor ruthenium red of the Ca2+ releasing channel of sarcoplasmic reticulum (SR) all exerted a profound inhibitory action on arsenite-contracture. Neither the Ca(2+)-release nor the Ca(2+)-ATPase activity of SR. were affected by 50 microM arsenite. These findings indicate a possibility that arsenite induced muscle contracture by enhancing Ca(2+)-entry which further induced Ca(2+)-release from SR. Moreover, the possible mechanism of twitch blockade induced by arsenite was studied by an electrophysiological technique. The frequency of miniature endplate potential (m.e.p.p.) was initially increased but eventually abolished by arsenite, while the amplitude of m.e.p.p. remained unaffected and that of endplate potential rapidly declined. It is considered that arsenite increased the spontaneous release of transmitter by enhancing Ca2+ entry into the nerve terminal and inhibited the evoked transmitter release possibly by acting at a certain site which governs transmitter release.
Hsu
K S
KS
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Kang
J J
JJ
Lin-Shiau
S Y
SY
D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D018053:Arsenites; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000187:drug effects; D003964:Diaphragm / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects
D018053:Arsenites; D000252:Calcium-Transporting ATPases; C015001:arsenite; D001151:Arsenic; D002118:Calcium