Pharmacologic and therapeutic aspects of the developmentally regulated expression of GABA(A) and GABA(B) receptors: cerebellar granule cells as a model system
- PMID: 10397364
- DOI: 10.1016/s0197-0186(99)00044-3
Pharmacologic and therapeutic aspects of the developmentally regulated expression of GABA(A) and GABA(B) receptors: cerebellar granule cells as a model system
Abstract
Cerebellar granule neurons can be conveniently kept in culture. They constitute a useful model to study regulation of glutamatergic activity, in particular the inhibitory action of GABA (7-aminobutyrate). GABA exerts an inhibitory action on evoked transmitter release acting on both GABA(A) and GABA(B) receptors. The functional properties of these receptors are dependent upon the environment of the neurons during early development in culture as the expression of both receptor subtypes is enhanced by exposure of the neurons to GABA(A) receptor agonists. Thus, the inducible GABA(A) receptors are of low affinity and lack benzodiazepine sensitivity, and the G-protein coupling differs among the native and the inducible GABA(B) receptors. Moreover, the GABA(A) and the GABA(B) receptors are functionally coupled, leading to a disinhibitory action of GABA. Therefore drugs exhibiting selective agonist or antagonist action on subclasses of GABA(A) and GABA(B) may be of potential use as regulators of glutamatergic excitatory activity.
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