Studies on the contracture inducing action of triphenyltin in the mouse diaphragm

• Published in: European journal of pharmacology 1994-11, Vol.292 (1), p.95-101
• Main Authors: Liu, Shing-Hwa, Lin-Shiau, Shoei-Yn
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Biological and medical sciences; Ca 2+-induced Ca 2+ release; Caffeine - pharmacology; Calcium - pharmacokinetics; Calcium - pharmacology; Calcium Radioisotopes; Chemical and industrial products toxicology. Toxic occupational diseases; Diaphragm; Diaphragm - drug effects; Diaphragm - physiology; Dithiothreitol - pharmacology; Drug Interactions; Egtazic Acid - pharmacology; Female; Glycerol - pharmacology; In Vitro Techniques; Male; Medical sciences; Membrane Potentials - drug effects; Metals and various inorganic compounds; Mice; Mice, Inbred ICR; Muscle Contraction - drug effects; Na +-channel activation; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; Organotin Compounds - toxicity; Potassium - pharmacology; Ryanodine - pharmacology; Tetrodotoxin - pharmacology; Toxicology; Triphenyltin-induced contracture; Trypsin - pharmacology; Veratridine - pharmacology
• ISSN: 0926-6917; 0014-2999
• DOI: 10.1016/0926-6917(94)90031-0

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 μM; a Na + channel activator) briefly shortened the onset of the contracture and increased the peak tension of the contracture. Pretreatment with tetrodotoxin (0.3 μM; a Na + channel blocker) or glycerol (a T tubule uncoupler), however, significantly reduced the triphenyltin-induced contracture. Removing Ca 2+ from external solution and prolonged treatment with either caffeine (20 mM) or ryanodine (2 μM) inhibited the triphenyltin-induced contracture. However, a brief treatment with a lower concentration of caffeine (10 mM) potentiated the contracture. 45Ca 2+ uptake studies showed that triphenyltin caused the muscle to accumulate Ca 2+ 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 Ca 2+ from sarcoplasmic reticulum through the mechanism of Ca 2+ inducing Ca 2+ release, activates the contractile filaments and causes the muscle to contract.