INHIBITION OF FAST-PHASE AND SLOW-PHASE DEPOLARIZATION-DEPENDENT SYNAPTOSOMAL CALCIUM-UPTAKE BY ETHANOL

  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (3) , 571-575
Abstract
Uptake of 45Ca2+ by synaptosomes isolated from cerebral cortex, cerebellum, midbrain and brain stem of male Sprague-Dawley rats was measured at 1-, 3-, 5-, 15-, 30- and 60-s time periods. At 1 s, The Ca2+ uptake rate by cerebrocortical synaptosomes was 1.45 .mu.mol/s per g of protein, whereas the 60-s rate was 0.03 .mu.mol/s per g of protein. In vitro addition of ethanol, 80 mM, inhibited depolarization-dependent (65 mM KCl) 45Ca2+ uptake by synaptosomes but the time-response relationships varied depending upon the brain region studied. In cerebrocortical synaptosomes, ethanol significantly inhibited only the fast-phase component of 45Ca2+ uptake (1 and 3 s). Ethanol inhibited 45Ca2+ uptake by midbrain synaptosomes at all measurement times studied (1, 3, 5 and 15 s), whereas in cerebellum and brain stem ethanol inhibited 45Ca2+ uptake at 3- and 5-s time periods. Ethanol at concentrations of 25, 50, 100 and 150 mM inhibited 45Ca2+ uptake by 9.0, 15.9, 24.8 and 30.7%, respectively, in cerebrocortical synaptosomes. In vitro ethanol, 80 mM, added to cerebrocortical synaptosomes isolated from rats fed a nutritionally adequate liquid ethanol diet, did not significantly inhibit depolarization-dependent 45Ca2+ uptake. Pharmacologically relevant ethanol concentrations evidently inhibit voltage-dependent 45Ca2+ uptake into synaptosomes. This inhibitory action may, at least in part, underlie some of the intoxicating effects of ethanol. Chronic administration of ethanol resulted in an apparent adaptive response such that addition of ethanol no longer blocked 45Ca2+ uptake. This adaptive response involving the Ca channel may represent a cellular mechanism for functional tolerance development.