Modulation by Zn2+ and Cd2+ of GABAA receptors of rat cerebellum granule cells in culture

This study aims to characterize more closely the different populations of GABA(A) receptors present on the cerebellar granule cells of the rat. The effects of two divalent cations, Zn(2+) and Cd(2+), on GABA-activated chloride currents were studied using the whole-cell patch-clamp technique. Zinc cations inhibit differently the peak and the steady-state current elicited by 10 micro M GABA. In fact, Zn(2+) appears to be more potent in inhibiting the steady-state component, with a lower IC(50). The inhibition of the peak component is of the competitive type, whereas the inhibition of the steady-state one is mixed, being partly competitive and partly allosteric. In addition, Cd(2+) has an inhibitory effect on GABA-activated chloride currents. In terms of the peak component, its effect is limited in extent with a maximal inhibition of only 26%, but with a high affinity (IC(50) as low as 0.03 micro M). The steady-state component is inhibited by 20% independently from the Cd(2+) concentration, in the 10(-2)-10(2) micro M range. In this case, the inhibitory mechanism appears to be of the competitive type for the peak component and of the allosteric type for the steady-state one. We suggest these data are a further confirmation that the rapidly and slowly desensitizing components of the GABA-activated chloride currents, corresponding respectively to the peak and the steady-state components, are made up of two different receptor populations.