The possible roles of Na+ and Ca2+ overload in the mechanism of monesin-induced myotoxicity is isolated avian (Gallus domesticus) skeletal muscle

DA Sandercock*, MA Mitchell

*Corresponding author for this work

Research output: Contribution to journalMeeting Abstractpeer-review


Monensin is a sodium-selective ionophore widely employed therapeutically as an antibiotic and coccidiostat in domestic species; however, myopathy and myonecrosis associated with treatment have been frequently reported (Dowling, 1992). Disturbances in the regulation of intracellular calcium ([Ca2+]i) are implicated in the development of tissue damage (Nicotera et al. 1992). The present study has therefore attempted to characterize the possible mechanisms involving altered calcium homeostasis in mediating the effects of monensin upon skeletal muscle. Wing web muscles (M. tensor brevis) were removed from 4-week-old broiler chickens killed by i.v. injection of sodium pentobarbitone. Tissues were incubated in medium 199 at 41.5°C for up to 2.5 h. Muscle damage was assessed by the efflux of the intracellular enzyme creatine kinase (CK). Calcium accumulation was estimated by inclusion of 45Ca2+ (16.4 kBq ml-1) in the medium. Both 45Ca2+ uptake and CK efflux increased with ionophore concentration. Monensin (100 µM) induced a maximal 8-fold increase in CK loss (P<0.001, ANOVA) concomitant with an 80% stimulation of 45Ca2+ accumulation (P<0.05). Inhibition of sodium extrusion by 2 mM ouabain produced further significant increases (P< 0.001) in 45Ca2+ uptake (93%) and CK efflux (2.6-fold) in monensin-treated muscles. Reduction of extracellular ionic calcium by addition of 5 mM BAPTA (1, 2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid) decreased 45Ca2+ uptake by 48% (P<0.001), but produced a 2.4-fold increase (P<0.001) in CK efflux. Incubation with 15 µM thapsigargin in the absence of extracellular calcium (5 mm BAPTA) resulted in a 279-fold increase (P<0.001) in CK release whilst dantrolene (100 µM) inhibited the monensin-induced enzyme efflux by 52% (P<0.001) in the presence of normal external calcium concentration. It is proposed that elevation of intracellular sodium by monensin may promote entry of calcium and thus cell damage and CK release possibly by increased Na+-Ca2+ exchange. Stimulation of enzyme efflux, however, does not require influx of extracellular calcium but may be mediated by redistribution of Ca2+i stores, perhaps involving altered function of the sarcoplasmic reticulum. It is likely that both these systems are active concurrently at high [Na+]j. Dantrolene may offer a therapeutic strategy in the treatment of monensin myotoxicity.
Dowling, L. (1992). Avian Pathology 21, 353-368.
Nicotera, P., Bellomo, G. & Orrenius, S. (1992). Ann. Rev. Pharmacol. Toxicol. 32, 449-470.
Original languageEnglish
Pages (from-to)41-42P
Number of pages2
JournalJournal of Physiology
Issue numberSupplement
Publication statusPrint publication - 1995
Externally publishedYes
EventThe Physiological Society Annual Meeting 1995 - University of Keele, Keele, United Kingdom
Duration: 19 Apr 199521 Apr 1995


  • Monensin-induced myotoxicity
  • Sodium ionophore
  • Sodium ions
  • Calcium ions
  • Broiler chicken
  • Gallus domesticus
  • Skeletal muscle
  • Intracellular calcium regulation
  • Creatine kinase
  • Muscle enzyme efflux
  • Ouabain
  • Thapsigargin
  • Sarcoplasmic reticulum
  • Na+-Ca2+ exchanger


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