NA-DEFICIENT CONDITIONS IN RESPONSE TO ELECTRICAL-FIELD DEPOLARIZATION( INFLUX THROUGH CA2+ CHANNELS CAN PROMOTE STRIATAL GABA EFFLUX IN CA2+)

Electrical field depolarization releases gamma-aminobutyric acid (GABA ) in rat striatal slices in the absence of external Ca2+. omega-Conoto xin GVIA (omega-CgTx; 1-50 nM), a neuronal Ca2+ channel blocker, inhib its electrically evoked efflux of newly taken up [H-3]GABA in a concen tration-dependent manner in either normal or Ca2+-free medium. This su ggests that ion influx occurs through Ca2+ channels in the absence of external Ca2+ and contributes to the afflux of GABA. Reducing external Na+ concentration to 27.25 mM (low [Na+](o) medium) by equimolarly su bstituting choline chloride for sodium chloride has differential effec ts on electrically evoked GABA efflux depending on the external Ca2+ c oncentrations. In normal Ca2+ medium, electrically evoked GABA efflux increases whereas, in Ca2+-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 me dium, resting GABA efflux increases 17-fold whereas evoked GABA efflux diminishes. In Ca2+-free medium, 70 min of incubation with 2-bis-(2-a minophenoxy)ethane-N,N,N',N'tetraacetoxy methyl ester (BAPTA-AM, 1 mu M), an intracellular calcium chelator, increases both resting GABA eff lux and electrically evoked GABA overflow by similar to 100%. These re sults suggest that: (1) in Ca2+-free conditions, Na+ permeability of c ells increases via Ca2+ channels and this profoundly affects GABA effl ux. (2) Electrical field depolarization is likely to release GABA by d irectly depolarizing axon terminals. (3) Ca2+-independent GABA efflux is not promoted by an increase in intracellular free Ca2+ concentratio n via Na+/Ca2+ exchange processes from internal pools.