Regulation of putative Ca2+ channels in the brain

Ca2+ entry mechanisms were studied in a variety of neuronal preparations. In synaptosomes and intact brain cells K+-induced Ca2+ entry is a biphasic process. Highest density of both processes is found in the hippocampus and the lowest in the cerebellum. The slow second phase shows no regional distribution, is abolished in Na+ free medium and is antagonized by 3,4-dichlorobenzamil. It therefore likely represents Ca2+ influx through the Na+/Ca2+ exchanger. The chronic treatment of rats with atropine or diisopropyl phosphororfluoridate (DFP) led to an increase or decrease of 30% and 50% respectively, in the number of muscarinic receptors in the brain. In a similar fashion chronic administration of propranolol increased β-adrenoceptors 69% and 50% in brain and heart respectively. Isoproterenol administration decreased β-adrenoceptors by 50% in heart, but had no effect in the brain. None of these protocols had an effects on the number of Ca2+ channel binding sites as detected by [3H]nimodipine. Ethanol inhibits the first phase of synaptosomal 45Ca2+ uptake to a greater extent than the second phase. 45Ca2+ uptake in PC12 cells is inhibited in a similar fashion to that of the first phase. Chronic exposure to ethanol led to a 44% increase in 45Ca2+ uptake and a 38% increase in binding sites. This suggests that long-term antagonism of Ca2+ channels may lead to an increase in their numbers