GABA-B-MEDIATED MODULATION OF IONIC CONDUCTANCES IN TYPE-I HAIR-CELLSISOLATED FROM GUINEA-PIG SEMICIRCULAR CANALS

Mammalian vestibular type I hair cells (VIHCs) are innervated by an af ferent synaptic calyx which contains vesicles and is immunoreactive fo r GABA. We describe here the effects of GABA on electrophysiological p roperties and on cytosolic free-calcium levels ([Ca2+]i) of VIHCs isol ated from guinea-pig ampullae. Whole-cell tight-seal macroscopic curre nts recorded from VIHCs showed that 100 muM GABA induced a decrease in the outward currents elicited by depolarizing membrane potentials. Th ese are known to comprise potassium calcium-dependent currents. This e ffect was mimicked by baclofen, a GABA(B) agonist, and was not affecte d by picrotoxin, a GABA(A) antagonist. GABA also induced an increase i n the inward current elicited at hyperpolarized membrane potentials in 50% of the tested cells. Single channel recording in cell-attached pa tches revealed that externally applied GABA produced a decrease and an increase in the open probability of 170 pS and 45 pS and of 15 pS cha nnels, respectively. In imaging experiments using the dye Fura-2 to me asure [Ca2+]i, the only reversible modulation of [Ca2+]i observed in r esponse to GABA application was a decrease. These results demonstrate a modulation of calcium and potassium conductances by GABA, via GABA(B ) receptors, in guinea-pig VIHCs.