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 homome ric 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 K-d approximate to 1 mu M . The properties of these GABA(rho 1) receptors were similar to those of native bicuculline-resistant GABA receptors expressed by retinal mR NA. GABA(rho 1) currents showed very little desensitization, were bloc ked by picrotoxin but not by bicuculline, and were not modulated by ba rbiturates, benzodiazepines, or beta-carbolines. Zn2+ reversibly decre ased GABA(rho 1) responses (IC50 = 22 mu M). Other divalent cations we re also tested and their rank order of potency was: Zn2+ approximate t o Ni2+ approximate to Cu2+ >> Cd2+, whereas Ba2+, Co2+, Sr2+, Mn2+, Mg 2+, and Ca2+ showed little or no effect. In contrast, La3+ reversibly potentiated the GABA currents mediated by homomeric GABA(rho) receptor s, with an EC(50) = 135 mu M and a maximal potentiation of about 100% (GABA, 1 mu M; 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 particula r, Zn2+ may play a role during synaptic transmission in the retina.