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Bidirectional modulation of GABA-gated chloride channels by divalent cations: inhibition by Ca2+ and enhancement by Mg2+.

Publication ,  Journal Article
Schwartz, RD; Wagner, JP; Yu, X; Martin, D
Published in: J Neurochem
March 1994

The effects of the divalent cations Ca2+, Sr2+, Ba2+, Mg2+, Mn2+, and Cd2+ were studied on gamma-aminobutyric acidA (GABAA) responses in rat cerebral cortical synaptoneurosomes. The divalent cations produced bidirectional modulation of muscimol-induced 36Cl- uptake consistent with their ability to permeate and block Ca2+ channels. The order of potency for inhibition of muscimol responses was Ca2+ > Sr2+ > Ba2+, similar to the order for permeation of Ca2+ channels in neurons. The order of potency for enhancement of muscimol responses was Cd2+ > Mn2+ > Mg2+, similar to the order for blockade of Ca2+ channels in neurons. Neither Ca2+ nor Mg2+ caused accumulation of GABA in the extravesicular space due to increased GABA release or decreased reuptake of GABA by the synaptoneurosomes. The inhibition of muscimol responses by Ca2+ was most likely via an intracellular site of action because additional inhibition could be obtained in the presence of the Ca2+ ionophore, A23187. This confirms electrophysiologic findings in cultured neurons from several species. In contrast, the effects of Cd2+, Mn2+, and Mg2+ may be mediated via blockade of Ca2+ channels or by intracellular sites, although the results of these studies do not distinguish between the two loci. The effects of Zn2+ were also studied, because this divalent cation is reported to have widely divergent effects on GABAA responses. In contrast to other studies, we demonstrate that Zn2+ inhibits GABAA responses in an adult neuronal preparation. Zn2+ produced a concentration-dependent inhibition (limited to 40%) of muscimol responses with an EC50 of 60 microM. The inhibition of muscimol-induced 36Cl- uptake by Zn2+ was noncompetitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Published In

J Neurochem

DOI

ISSN

0022-3042

Publication Date

March 1994

Volume

62

Issue

3

Start / End Page

916 / 922

Location

England

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Zinc
  • Synaptosomes
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Muscimol
  • Male
  • Magnesium
  • Ion Channel Gating
 

Citation

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ICMJE
MLA
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Schwartz, R. D., Wagner, J. P., Yu, X., & Martin, D. (1994). Bidirectional modulation of GABA-gated chloride channels by divalent cations: inhibition by Ca2+ and enhancement by Mg2+. J Neurochem, 62(3), 916–922. https://doi.org/10.1046/j.1471-4159.1994.62030916.x
Schwartz, R. D., J. P. Wagner, X. Yu, and D. Martin. “Bidirectional modulation of GABA-gated chloride channels by divalent cations: inhibition by Ca2+ and enhancement by Mg2+.J Neurochem 62, no. 3 (March 1994): 916–22. https://doi.org/10.1046/j.1471-4159.1994.62030916.x.
Schwartz, R. D., et al. “Bidirectional modulation of GABA-gated chloride channels by divalent cations: inhibition by Ca2+ and enhancement by Mg2+.J Neurochem, vol. 62, no. 3, Mar. 1994, pp. 916–22. Pubmed, doi:10.1046/j.1471-4159.1994.62030916.x.
Journal cover image

Published In

J Neurochem

DOI

ISSN

0022-3042

Publication Date

March 1994

Volume

62

Issue

3

Start / End Page

916 / 922

Location

England

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Zinc
  • Synaptosomes
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Muscimol
  • Male
  • Magnesium
  • Ion Channel Gating