Modulation of ACh release at the efferent-IHC synapse by the Gabaergic system

WEDEMEYER, C; ZORRILLA DE SAN MARTIN, J.; BALLESTERO, J.; ELGOYHEN, A.B; KATZ, E.

Villa Carlos Paz, Cordoba, Argentina

Congreso; XLIV Reunion Anual de la Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2008

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

Before the onset of hearing, inner hair cells (IHC) of the mammalian cochlea are transiently innervated by medial olivocohlear (MOC) efferent fibers. This synapse is cholinergic, inhibitory and mediated by the á9á10 nicotinic receptor. Although ACh is the main transmitter released at this synapse, there is evidence showing that the GABA is present at MOC synaptic terminals and that GABAA receptors are expressed in outer hair cells (OHC). However, no GABAergic currents have been recorded so far in IHC or OHC. Moreover, the possibility that synaptically released GABA could be modulating the cholinergic input at MOC-synapses by acting on presynaptic GABAB receptors has not been investigated yet.  In the present work, we therefore evaluated the effects of a GABAB antagonist (CGP34358) on the quantal content of transmitter release at the MOC-IHCsynapse. Postsynaptic cholinergic currents, evoked by electrically stimulating the efferent fibers, were recorded in voltage-clamped (-90 mV) IHCs from acutely isolated mouse organs of Corti. The quantal content of evoked release was significantly increased by 0.3 mM CGP34358 (60 ± 2.3% p< 0.001). The lack of effect of  CGP34358 on spontaneous synaptic current amplitude indicates that the site of action of this drug is presynaptic. Our results suggest that GABA might be exerting a negative feedback control on the release of ACh at this synapse.