GABAA Receptors of Cerebellar Granule Cells in Culture: Interaction with Benzodiazepines

Abstract

GABA receptor mediated inhibition plays an important role in modulating the input/output dynamics of cerebellum. A characteristic of cerebellar GABA receptors is the presence in cerebellar granule cells of subunits such as α6 and δ which give insensitivity to classical benzodiazepines. In fact, cerebellar GABA receptors have generally been considered a poor model for testing drugs which potentially are active at the benzodiazepine site. In this overview we show how rat cerebellar granule cells in culture may be a useful model for studying new benzodiazepine site agonists. This is based on the pharmacological separation of diazepam-sensitive α1 β2/3 γ2 receptors from those which are diazepam-insensitive and contain the α6 subunit. This is achieved by utilizing furosemide/Zn which block α6 containing and incomplete receptors.

Involvement of GABAA receptors containing α6 subtypes in antisecretory factor activity on rat cerebellar granule cells studied by two‐photon uncaging

“…CGCs in primary culture are mainly composed of α 1 , α 6 , β 2/3 , γ 2 and δ subunits. Previous studies (Cupello et al, 2013;Gatta et al, 2009) showed that the GABA A subtypes that contribute to the peak current are α 1 β 2/3 γ 2 , α 6 β 2/3 γ 2 + α 1 α 6 β 2/3 γ 2 and α 6 β 2/3 incomplete receptors. So studying the peak current variations, induced by AF-16, means investigating its effects on these subtypes.…”

“…It appears of interest to study in model systems with well‐characterized GABA A receptors the effects of the AF in order to build a framework of knowledge allowing to conceive and test hypotheses about the roles of GABA in the AF anti‐hypersecretory activity via GABA A receptors of enteric ganglia. Based on a long experience with GABA A receptors of cerebellar granule cells (CGCs) in primary cultures (Cupello et al, 2013; Robello et al, 1993), we studied the effects of AF on those GABA A receptors. In addition, in this context, the CGC model is interesting from another point of view.…”

“…The rationale of the experiments was to understand which GABA A subtypes were involved in the receptor response after AF‐16 incubation, considering that α 6 subunits mainly characterize CGCs GABA A receptors (Cupello et al, 2013; Gatta et al, 2009).…”