Alcohol and local anesthetic effects on Na+-dependent Ca2+ fluxes in brain synaptic membrane vesicles.
Resealed synaptic plasma membrane vesicles exhibit Na+-dependent Ca2+ transport activity which may participate in regulation of free Ca2+ concentrations in nerve endings. Sodium chloride-loaded vesicles took up Ca2+ from the external medium (150 mM KCl-25 mM Tris/HCl) in the presence of an outward-directed Na+ gradient, a Ca2+ concentration of 38.6 microM producing half-maximal uptake at 23 degrees. Methanol (5-200 mM) and low concentrations of ethanol (5-25 mM) enhanced the Na+-dependent Ca2+ influx measured at 23 degrees. Higher ethanol concentrations (100-600 mM), as well as 1-propanol and 1-butanol (10-200 mM), produced only inhibition of Ca2+ fluxes. Dixon plot analysis of the inhibitory phase revealed that ethanol inhibited Ca2+ uptake in an apparently competitive manner with respect to Ca2+ concentration, and the Ki obtained from these experiments was 1.01 M ethanol. The inhibition of Ca2+ fluxes by butanol was non-competitive, and the Ki was 68.6 mM. The local anesthetics dibucaine and tetracaine also inhibited Ca2+ fluxes with IC50 values of 1.8 mM for tetracaine and 0.46 mM for dibucaine. The possible physiologic consequences of this inhibition of Na+-Ca2+ countertransport is synaptic membranes by the alcohols and local anesthetics are discussed with regard to neuronal transmission and membrane conductance.
D000438:Alcohols / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*
D000438:Alcohols; D000779:Anesthetics, Local; D007473:Ion Channels; D000431:Ethanol; D012964:Sodium; D002118:Calcium