Characterization of the Effect of Monensin on ?-Amino-n-Butyric Acid Release from Isolated Nerve Terminals

Abstract

The action of the polyether antibiotic monensin on the release of .gamma.-[3H]amino-n-butyric acid ([3H]GABA) from mouse brain synaptosomes is characterized. Monensin enhances the release of this amino acid transmitter in a dose-dependent manner and does not modify the efflux of the nontransmitter amino acid .alpha.-[3H]aminoisobutyrate. The absense of external Ca2+ fails to prevent the stimulatory effect of monoensin on [3H]GABA release. Furthermore, monensin is less effective in stimulating [3H]GABA release in the presence of Ca2+. The releasing response to monensin is absolutely dependent on external Na+. The blockade of voltage-sensitive Na+ or Ca2+ channels does not modify monensin-induced release of the transmitter. Also, the blockade of the GABA uptake pathway fails to prevent the stimulatory effect of monensin on [3H]GABA release. Although monensin markedly increases Na+ permeability in synaptosomes, these data indicate that the Ca2+-independent monensin-stimulated uptake pathway. It is concluded that the entrance of Na+ through monensin molecules inserted in the presynaptic membrane might be sufficient to initiate the intraterminal molecular events underlying transmitter release.