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

Sandor Bernath, Michael J. Zigmond, Eric S. Nisenbaum, E. Vízi, Theodore W. Berger

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Electrical field depolarization releases γ-aminobutyric acid (GABA) in rat striatal slices in the absence of external Ca2+. ω-Conotoxin GVIA (ω-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 Ca2+-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+]0 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 Ca2+-free medium, it is greatly inhibited when [Na+]0 is reduced to 27.25 mM. In low [Na+]0 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 Ca2+-free medium, 70 min of incubation with 1-2-bis-(2-aminophenoxy)ethane-N,N,N′,N′ tetraacetoxy methyl ester (BAPTA-AM, 1 μM), an intracellular calcium chelator, increases both resting GABA efflux and electrically evoked GABA overflow by ∼100%. These results suggest that: (1) in Ca2+-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) Ca2+-independent GABA efflux is not promoted by an increase in intracellular free Ca2+ concentration via Na+/Ca2+ exchange processes from internal pools.

Original languageEnglish
Pages (from-to)232-238
Number of pages7
JournalBrain Research
Volume632
Issue number1-2
DOIs
Publication statusPublished - Dec 31 1993

Fingerprint

Corpus Striatum
gamma-Aminobutyric Acid
Conotoxins
Aminobutyrates
Ethane
Tetrodotoxin
Presynaptic Terminals
Choline
Sodium Chloride

Keywords

  • Antidromic stimulation
  • BAPTA-AM
  • Na permeability
  • Neostriatum
  • γ-Aminobutyric acid
  • ω-Conotoxin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Na+ influx through Ca2+ channels can promote striatal GABA efflux in Ca2+-deficient conditions in response to electrical field depolarization. / Bernath, Sandor; Zigmond, Michael J.; Nisenbaum, Eric S.; Vízi, E.; Berger, Theodore W.

In: Brain Research, Vol. 632, No. 1-2, 31.12.1993, p. 232-238.

Research output: Contribution to journalArticle

Bernath, Sandor ; Zigmond, Michael J. ; Nisenbaum, Eric S. ; Vízi, E. ; Berger, Theodore W. / Na+ influx through Ca2+ channels can promote striatal GABA efflux in Ca2+-deficient conditions in response to electrical field depolarization. In: Brain Research. 1993 ; Vol. 632, No. 1-2. pp. 232-238.
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AB - Electrical field depolarization releases γ-aminobutyric acid (GABA) in rat striatal slices in the absence of external Ca2+. ω-Conotoxin GVIA (ω-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 Ca2+-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+]0 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 Ca2+-free medium, it is greatly inhibited when [Na+]0 is reduced to 27.25 mM. In low [Na+]0 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 Ca2+-free medium, 70 min of incubation with 1-2-bis-(2-aminophenoxy)ethane-N,N,N′,N′ tetraacetoxy methyl ester (BAPTA-AM, 1 μM), an intracellular calcium chelator, increases both resting GABA efflux and electrically evoked GABA overflow by ∼100%. These results suggest that: (1) in Ca2+-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) Ca2+-independent GABA efflux is not promoted by an increase in intracellular free Ca2+ concentration via Na+/Ca2+ exchange processes from internal pools.

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