BARIUM-EVOKED GLUTAMATE RELEASE FROM GUINEA-PIG CEREBROCORTICAL SYNAPTOSOMES

Ba2+ has multiple effects on presynaptic terminals. The ion inhibits t he K+ channels responsible for stabilizing the plasma membrane potenti al in the same way as previously reported for dendrotoxin and 4-aminop yridine. Secondly, the ion can substitute fully for Ca2+ in supporting KCl-evoked release of glutamate from guinea-pig cerebrocortical synap tosomes. In the latter case, the kinetics of glutamate release in the presence of saturating Ca2+ or Ba2+ are essentially identical. Substan tially lower external concentrations of Ba2+ are required to achieve t he same release kinetics as with Ca2+. The average internal free Ba2concentration attained during KCl depolarization is some 1 0-fold high er than that for Ca2+ . However, because the fura-2 signal reflects pr edominantly the overflow of divalent cation after dissociation from th e release trigger, it is not the valid parameter to compare effectiven ess of the cations in triggering glutamate exocytosis. In view of the established inability of Ba2+ to interact with calmodulin, these resul ts are discussed in relation to theories in which Ca2+/calmodulin-depe ndent protein kinase-mediated phosphorylation is a prerequisite for sy naptic vesicle exocytosis.