Regulation of the expression of low affinity GABA(A) receptors in rat cerebellar granule cells

GABA(A) receptors of cerebellar granule cells obtained from neonatal rats a nd 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 t wo binding components appear. The low affinity component seems to be the on e appearing later. The expression of this component seems to be regulated b y protein tyrosine phosphorylation. In fact, its expression is down regulat ed by the protein tyrosine kinase (PTK) inhibitor, genistein. Viceversa, it s expression is upregulated by insulin like growth factor I (IGF-I), most p robably via PTK activation. A possible interpretation of the data is that in vivo IGF-I is one of the e ndogenous messages leading to the expression of this component during devel opment. 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 probabl y correspond to extrasynaptic GABA(A) receptors mediating the tonic form of inhibition in cerebellar granules.