Effects of isoflurane on voltage-dependent calcium fluxes in rabbit T-Tubule membranes: Comparison with alcohols

摘要

The effects of racemic (+/-) and (+)- and (-)-stereoisomers of isoflurane on depolarization-induced Ca-45(2+) fluxes mediated by voltage-dependent Ca2+ channels were investigated in transverse tubule membrane vesicles from rabbit skeletal muscle. In the concentration range 0.5 to 2 mM, (+/-)-isoflurane inhibited Ca-45(2+) fluxes and functionally modulated the effects of the Ca2+ channel antagonist nifedipine (1-10 muM). Isoflurane-induced inhibition of Ca-45(2+) fluxes was not significantly affected by pretreatment with either pertussis toxin (5 mug/ml or phorbol 12-myristate 13-acetate (50 nM). Further experiments indicated that there were no significant differences between (+)- and (-)-stereoisomers of isoflurane with respect to the extent of inhibition of Ca-45(2+) fluxes. Radioligand binding studies indicated that racemic and (+)- and (-)-isoflurane were equally effective in displacing the specific binding of ['HIPN 200-110 to transverse tubule membranes. There were no apparent differences between the effects of (+)- and (-)-isoflurane on the characteristics of [H-3]PN 200-110 binding. Although the concentrations of isoflurane for the inhibitions of Ca-45(2+) fluxes and radioligand bindings were similar, the concentrations of n-alcohols required for the inhibition of Ca-45(2+) fluxes were lower than those for the displacement of radioligand. Comparison of the data for the displacement of [H-3]PN 200-110 binding and the inhibition of Ca-45(2+) fluxes by isoflurane and by n-alcohols suggested that both isoflurane and n-alcohols may have more than a single binding site. In conclusion, results indicate that isoflurane, independent of intracellular Ca2+ levels, nonstereospecifically inhibits the function of voltage-dependent Ca2+ channels and this effect is mediated through multiple binding sites. (C) 2002 Elsevier Science (USA). [References: 34]