Cis-4-amino-crotonic acid activates alpha 6 subunit-containing GABA(A) but not GABA(C) receptors in granule cells of adult rat cerebellar slices.

The expression of GABA(C) receptors in granule cells of adult rat cerebellar slices was investigated. The GABA(C) receptor agonist cis-4-amino-crotonic acid (CACA) evoked currents in granule cells. However, CACA-evoked currents were not blocked by the GABA(C) receptor antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA), but were blocked by the GABA(A) receptor antagonist bicuculline. CACA activated alpha6 subunit-containing GABA receptors as CACA-evoked currents were reduced by furosemide and CACA activated alpha6beta2gamma2s receptors expressed in HEK 293 cells. The channels opened by CACA had conductances which were larger than those described for GABA(C) receptors but were similar to those described for GABA(A) receptors. GABAergic synaptic currents were blocked by low concentrations of bicuculline, but not by TPMPA. Thus, cerebellar granule cells express functional GABA(A) but not GABA(C) receptors.