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.
Bernath
S
S
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Zigmond
M J
MJ
Nisenbaum
E S
ES
Vizi
E S
ES
Berger
T W
TW
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D020866:omega-Conotoxin GVIA; D012964:Sodium; D002118:Calcium