Cationic modulation of rho 1-type gamma-aminobutyrate receptors expressed in Xenopus oocytes.
A study was made of the effects of di- and trivalent cations on homomeric rho 1-type gamma-aminobutyrate (GABA rho 1) receptors expressed in Xenopus oocytes after injection of mRNA coding for the GABA rho 1 subunit. GABA elicited large currents with a Kd approximately 1 microM. The properties of these GABA rho 1 receptors were similar to those of native bicuculline-resistant GABA receptors expressed by retinal mRNA. GABA rho 1 currents showed very little desensitization, were blocked by picrotoxin but not by bicuculline, and were not modulated by barbiturates, benzodiazepines, or beta-carbolines. Zn2+ reversibly decreased GABA rho 1 responses (IC50 = 22 microM). Other divalent cations were also tested and their rank order of potency was: Zn2+ approximately Ni2+ approximately 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 rho 1 receptors, with an EC50 = 135 microM and a maximal potentiation of about 100% (GABA, 1 microM; La3+, 1 mM). Other lanthanides showed similar effects (Lu3+ > Eu3+ > Tb3+ > Gd3+ > Er3% > Nd3+ > La3+ > Ce3+). Thus, GABA rho 1 receptors contain sites for cationic recognition, and in particular, Zn2+ may play a role during synaptic transmission in the retina.
Calvo
D J
DJ
Department of Psychobiology, University of California, Irvine 92717-4550.
Vazquez
A E
AE
Miledi
R
R
D000818:Animals; D002412:Cations / Q000494:pharmacology*; D018118:Chloride Channels / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007811:Lanthanum / Q000494:pharmacology; D018079:Receptors, GABA / Q000502:physiology*; D012160:Retina / Q000737:chemistry; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology
D002412:Cations; D018118:Chloride Channels; D018079:Receptors, GABA; D007811:Lanthanum; D015032:Zinc