Effects of cartap on isolated mouse phrenic nerve diaphragm and its related mechanism

Jiunn Wang Liao, Jaw Jou Kang, Shing Hwa Liu, Chian Ren Jeng, Yu Wen Cheng, Chien-Ming Hu, San Fu Tsai, Shun Cheng Wang, Victor Fei Pang

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16 Citations (Scopus)

Abstract

Cartap, a nereistoxin analogue pesticide, is reported to have no irritation to eyes in rabbits. However, we have demonstrated recently that cartap could actually cause acute death in rabbits via ocular exposure. Our preliminary study with isolated mouse phrenic nerve diaphragms has shown that instead of neuromuscular blockade, cartap caused muscular contracture. The objective of the study was to examine the effect of cartap on the neuromuscular junction in more detail and to investigate its possible underlying mechanism with isolated mouse phrenic nerve diaphragms and sarcoplasmic reticulum (SR) vesicles. Cartap or nereistoxin at various concentrations was added in the organ bath with isolated mouse phrenic nerve diaphragm and both nerve- and muscle-evoked twitches were recorded. Instead of blocking the neuromuscular transmission as nereistoxin did, cartap caused contracture in stimulated or quiescent isolated mouse phrenic nerve diaphragm. Both the cartap-induced muscular contracture force and the time interval to initiate the contracture were dose-dependent. The contracture induced by cartap was not affected by the pretreatment of the diaphragm with the acetylcholine receptor blocker α-bungarotoxin; the Na+ channel blocker tetrodotoxin; or various Ca2+ channel blockers, NiCl2, verapamil, and nifedipine. On the contrary, the contracture was significantly inhibited when the diaphragm was pretreated with ryanodine or EGTA containing Ca2+ -free Krebs solution or in combination. This suggested that both internal and extracellular Ca2+ might participate in cartap-induced skeletal muscle contracture. Moreover, cartap inhibited the [3H]-ryanodine binding to the Ca2+ release channel of SR in a dose-dependent manner. Additionally, cartap could induce a significant reduction in Ca2+-ATPase activity of SR vesicles at a relatively high dose. The results suggested that cartap might cause the influx of extracellular Ca2+ and the release of internal Ca2+, with subsequent induction of muscular contracture in the isolated mouse phrenic nerve diaphragm. Based on these findings, we propose that the acute death of rabbits following ocular exposure to cartap might have resulted from respiratory failure secondary to diaphragm contracture.

Original languageEnglish
Pages (from-to)453-459
Number of pages7
JournalToxicological Sciences
Volume55
Issue number2
Publication statusPublished - 2000

Keywords

  • Ca release
  • Cartap
  • Muscular contracture

ASJC Scopus subject areas

  • Toxicology

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  • Cite this

    Liao, J. W., Kang, J. J., Liu, S. H., Jeng, C. R., Cheng, Y. W., Hu, C-M., Tsai, S. F., Wang, S. C., & Pang, V. F. (2000). Effects of cartap on isolated mouse phrenic nerve diaphragm and its related mechanism. Toxicological Sciences, 55(2), 453-459.