Studies on the contracture inducing action of triphenyltin in the mouse diaphragm.
Triphenyltin induces a contracture of the mouse phrenic nerve-diaphragm preparation. This contracture was not inhibited by (+)-tubocurarine, high magnesium or the absence of electrical stimulation. Triphenyltin (0.1 mM) reduced the muscle membrane potential, the amplitude of the muscle action potential and the muscle membrane input resistance. Pretreatment with high K+ (25 mM) or veratridine (1.5 microM; a Na+ channel activator) briefly shortened the onset of the contracture and increased the peak tension of the contracture. Pretreatment with tetrodotoxin (0.3 microM; a Na+ channel blocker) or glycerol (a T tubule uncoupler) however, significantly reduced the triphenyltin-induced contracture. Removing Ca2+ from external solution and prolonged treatment with either caffeine (20 mM) or ryanodine (2 microM) inhibited the triphenyltin-induced contracture. However, a brief treatment with a lower concentration of caffeine (10 mM) potentiated the contracture. 45Ca2+ uptake studies showed that triphenyltin caused the muscle to accumulate Ca2+ which entered from external solution. Pretreatment with trypsin and dithiothreitol (a sulfhydryl-containing reducing agent) blocked the contracture induced by triphenyltin. These results suggest that triphenyltin initially interacts with the sulfhydryl groups of membrane bound proteins (possibly the Na+ channel) to cause depolarization of the muscle fibres. This depolarization triggers the release of Ca2+ from sarcoplasmic reticulum through the mechanism of Ca2+ inducing Ca2+ release, activates the contractile filaments and causes the muscle to contract.
Liu
S H
SH
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, ROC.
Shiau
S Y
SY
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D002132:Calcium Radioisotopes; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology; D004229:Dithiothreitol / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005990:Glycerol / Q000494:pharmacology; 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 / Q000502:physiology; D009947:Organotin Compounds / Q000633:toxicity*; D011188:Potassium / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D002132:Calcium Radioisotopes; D009947:Organotin Compounds; D012433:Ryanodine; D002110:Caffeine; D013779:Tetrodotoxin; D004533:Egtazic Acid; D014701:Veratridine; C030665:triphenyltin; D014357:Trypsin; D005990:Glycerol; D011188:Potassium; D002118:Calcium; D004229:Dithiothreitol