Cationic modulation of ρ1-type γ-aminobutyrate receptors expressed in Xenopus oocytes

Daniel J. Calvo, Ana E. Vazquez, Ricardo Miledi

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

A study was made of the effects of di- and trivalent cations on homomeric ρ1-type γ-aminobutyrate (GABA(ρ1)) receptors expressed in Xenopus oocytes after injection of mRNA coding for the GABA(ρ1) subunit. GABA elicited large currents with a K(d) ≃ 1 μM. The properties of these GABA(ρ1) receptors were similar to those of native bicuculline-resistant GABA receptors expressed by retinal mRNA. GABA(ρ1) currents showed very little desensitization, were blocked by picrotoxin but not by bicuculline, and were not modulated by barbiturates, benzodiazepines, or β-carbolines. Zn2+ reversibly decreased GABA(ρ1) responses (IC50 = 22 μM). Other divalent cations were also tested and their rank order of potency was: Zn2+ ≃ Ni2+ ≃ Cu2+ >> Cd2+, whereas Ba2+, Co2+, Sr2+, Mn2+, Mg2+, and Ca2+ showed little or no effect. In contrast, La3+ reversibly potentiated the GABA currents mediated by homomeric GABA(ρ1) receptors, with an EC50 = 135 μM and a maximal potentiation of about 100% (GABA, 1 μM; La3+, 1 mM). Other lanthanides showed similar effects (Lu3+ > Eu3+ > Tb3+ > Gd3+ > Er3+ > Nd3+ > La3+ > Ce3+). Thus, GABA(ρ1) receptors contain sites for cationic recognition, and in particular, Zn2+ may play a role during synaptic transmission in the retina.

Original languageEnglish (US)
Pages (from-to)12725-12729
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number26
DOIs
StatePublished - Dec 20 1994

Keywords

  • chloride channels
  • La potentiation
  • retina receptors
  • Zn inhibition

ASJC Scopus subject areas

  • Genetics
  • General

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