title: Modulation by Zn(2+) and Cd(2+) of GABA(A) receptors of rat cerebellum granule cells in culture.
abstract: 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.
authors.affiliation: INFM, Dipartimento di Fisica, Università di Genova, Via Dodecaneso 33, 16146 Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Casagrande
authors.forename: L
authors.initials: L
authors.lastname: Valle
authors.forename: A
authors.initials: A
authors.lastname: Cupello
authors.forename: M
authors.initials: M
authors.lastname: Robello
mesh_terms: D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; D011963:Receptors, GABA-A; D002104:Cadmium; D005680:gamma-Aminobutyric Acid; D015032:Zinc