Regulation of the expression of low affinity GABA_A receptors in rat cerebellar granule cells

Summary.

GABA_A receptors of cerebellar granule cells obtained from neonatal rats and kept in culture were studied by labelled muscimol binding.

The data show that, according to the maturational state of those cells in vivo, one or two binding components appear. The low affinity component seems to be the one appearing later. The expression of this component seems to be regulated by protein tyrosine phosphorylation. In fact, its expression is down regulated by the protein tyrosine kinase (PTK) inhibitor, genistein. Viceversa, its expression is upregulated by insulin like growth factor I (IGF-I), most probably via PTK activation.

A possible interpretation of the data is that in vivo IGF-I is one of the endogenous messages leading to the expression of this component during development. Another endogenous factor involved may be GABA itself.

Low affinity GABA_A receptors appear to be the ones involved in inhibitory synaptic transmission at glomeruli. Whereas the high affinity ones probably correspond to extrasynaptic GABA_A receptors mediating the tonic form of inhibition in cerebellar granules.