Direct inhibition of voltage-dependent Ca2+ fluxes by ethanol and higher alcohols in rabbit T-tubule membranes

Murat Oz, Yulia B. Tchugunova, Susan M.J. Dunn

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20 Citations (Scopus)


The effects of ethanol and higher alcohols on 45Ca2+ fluxes, mediated by voltage-dependent Ca2+ channels (VDCCs), were investigated in inside-out transverse (T)-tubule membrane vesicles from rabbit skeletal muscle. 45Ca2+ effluxes were induced by membrane potentials generated via establishing K+ gradients across the vesicles, and were significantly inhibited by the inorganic Ca2+ channel blocker La3+ (1 mM) and the Ca2+ channel antagonist nifedipine (1-10 μM). Ethanol, in the concentration range of 100-400 mM, caused a significant suppression of depolarization-induced 45Ca2+ fluxes. Ethanol also functionally modulated the effect of nifedipine (1-10 μM) and the Ca2+ channel agonist Bay K 8644 (1 μM) on Ca2+ effluxes. Pretreatment with pertussis toxin (5 μg/ml) or phorbol 12-myrstate 13-acetate (PMA, 50 nM) did not affect the ethanol inhibition of 45Ca2+ fluxes. Further experiments with alcohols revealed that butanol, hexanol, octanol and decanol also significantly inhibited 45Ca2+ effluxes. However, undecanol and dodecanol did not cause any significant change on 45Ca2+ fluxes, indicating that the effects of alcohols on 45Ca2+ effluxes exhibit a cut-off phenomenon. In radioligand binding studies, it was found that at the concentrations used in flux studies, alcohols did not alter the characteristics of the specific binding of [3H]PN 200-110 to T-tubule membranes. Results indicate that ethanol directly inhibits the function of voltage-dependent Ca2+ channels without modulating the specific binding of Ca2+ channel ligands of the dihydropyridine class, and that this inhibition is independent of intracellular Ca2+ levels.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number3
Publication statusPublished - Apr 27 2001
Externally publishedYes


  • Alcohol
  • Ca channel
  • Ethanol
  • Skeletal muscle

ASJC Scopus subject areas

  • Pharmacology


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