Ca2+ Transport by Intact Synaptosomes: the Voltage‐Dependent Ca2+ Channel and a Re‐evaluation of the Role of Sodium/Calcium Exchange

Abstract

The verapamil-sensitive Ca²⁺ channel in the synaptosomal plasma membrane is investigated. Verapamil is without effect on Ca²⁺ uptake or steady-state content in synaptosomes with a polarized plasma membrane, but completely inhibits the additional Ca²⁺ uptake following plasma-membrane depolarization by high [K⁺], by veratridine plus ouabain or by high concentrations of the permeant cation tetraphenylphosphonium. Verapamilinsensitive Ca²⁺ influx and steady-state content are identical in polarized and depolarized synaptosomes, even though the Na⁺ electrochemical potential is greatly decreased in the latter, indicating that Na⁺/Ca²⁺ exchange is not a significant mechanism for Ca²⁺ efflux under these conditions. A transient Na⁺-dependent Ca²⁺ efflux can only be observed on addition of Na⁺ to Na⁺-depleted, depolarized synaptosomes. While 0.2 mM verapamil decreases the rate of ⁸⁶Rb⁺ efflux and ²²Na⁺ entry during depolarization induced by veratridine plus ouabain, the final steady-state Nat accumulation is not inhibited. Ca²⁺ efflux from synaptosomes following mitochondrial depolarization does not occur by a verapamil-sensitive pathway.