Na+ influx through Ca2+ channels can promote striatal GABA efflux in Ca(2+)-deficient conditions in response to electrical field depolarization.

Electrical field depolarization releases gamma-aminobutyric acid (GABA) in rat striatal slices in the absence of external Ca2+. omega-Conotoxin GVIA (omega-CgTx; 1-50 nM), a neuronal Ca2+ channel blocker, inhibits electrically evoked efflux of newly taken up [3H]GABA in a concentration-dependent manner in either normal or Ca(2+)-free medium. This suggests that ion influx occurs through Ca2+ channels in the absence of external Ca2+ and contributes to the efflux of GABA. Reducing external Na+ concentration to 27.25 mM (low [Na+]o medium) by equimolarly substituting choline chloride for sodium chloride has differential effects on electrically evoked GABA efflux depending on the external Ca2+ concentrations. In normal Ca2+ medium, electrically evoked GABA efflux increases whereas, in Ca(2+)-free medium, it is greatly inhibited when [Na+]o is reduced to 27.25 mM. In low [Na+]o medium, GABA efflux is largely tetrodotoxin (TTX)-sensitive, however, spike firing evoked by antidromic stimulation of striatal cells is inhibited. In Na(+)-free medium, resting GABA efflux increases 17-fold whereas evoked GABA efflux diminishes. In Ca(2+)-free medium, 70 min of incubation with 1-2-bis-(1-aminophenoxy)ethane-N,N,N',N' tetraacetoxy methyl ester (BATPA-AM, 1 microM), an intracellular calcium chelator, increases both resting GABA efflux and electrically evoked GABA overflow by approximately 100%. These results suggest that: (1) in Ca(2+)-free conditions, Na+ permeability of cells increases via Ca2+ channels and this profoundly affects GABA efflux. (2) Electrical field depolarization is likely to release GABA by directly depolarizing axon terminals. (3) Ca(2+)-independent GABA efflux is not promoted by an increase in intracellular free Ca2+ concentration via Na+/Ca2+ exchange processes from internal pools.