Enhanced [3H]-noradrenaline release in synaptosomes from ethanol-tolerant animals: the role of nerve terminal calcium ion concentrations.
Cortical slices from brains of ethanol-tolerant rats have previously been shown to release a greater fraction of uptake [3H]-noradrenaline ([3H]-NA) on K+-depolarisation than slices from control animals. In the present experiments, when stimulated with the Ca2+ ionophore A23187 (30 microM), untreated cortical synaptosomes release only a very small fraction of uptaken [3H]-NA. Under these conditions synaptosomal preparations from ethanol-tolerant animals released a greater fraction of uptaken [3H]-NA but the difference was not significant. However, after incubation with ouabain (100 microM, to increase intrasynaptosomal [Ca2+]) A23187 now produced a much greater enhancement of [3H]-NA release in preparations from ethanol-tolerant rats. Further, after superfusion of the synaptosomal preparation with 1mM EGTA and A23187 for 30 min (a procedure which should reduce intrasynaptosomal [Ca2+]) the reintroduction of Ca2+ to the superfusing fluid caused a marked release of [3H]-NA which was also significantly greater in preparations from ethanol-tolerant animals. Ca2+/Mg2+-ATPase activity was also higher in these synaptosomes but no difference could be detected in the release of [3H]-NA from a combined synaptic vesicle: synaptic plasma membrane preparation. The results suggest that the development of ethanol tolerance is associated with a fundamental change in the dynamic control of Ca2+ concentrations within the nerve terminal which potentiates the depolarisation-induced release of neurotransmitters.
M A
MA
Lynch
J M
JM
Littleton
D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology; D004361:Drug Tolerance; D006801:Humans; D007473:Ion Channels / Q000201:enzymology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013570:Synaptic Membranes / Q000201:enzymology; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000201:enzymology; D013574:Synaptosomes / Q000201:enzymology*
D007473:Ion Channels; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D009638:Norepinephrine