Modulation of ACh release at the efferent-IHC synapse by presynaptic GABAB receptors.

CAROLINA WEDEMEYER; JIMENA BALLESTERO; JAVIER ZORRILLA DE SAN MARTÍN; ANA BELÉN ELGOYHEN; ELEONORA KATZ

Villa Carlos Paz, Córdoba, Argentina

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

&lt;!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} pre {margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Courier New"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&gt; Before the onset of hearing, inner hair cells (IHC) of the mammalian cochleaare transiently innervated by medial olivocohlear (MOC) efferent fibers.This synapse is cholinergic, inhibitory and mediated by the alpha9alpha10nicotinic receptor. Although ACh is the main transmitter released at thissynapse, there is evidence showing that the GABA is present at MOC synapticterminals 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 bemodulating the cholinergic input at MOC-synapses by acting on presynapticGABAB receptors has not been investigated yet.  In the present work, wetherefore evaluated the effects of a GABAB antagonist (CGP55845) on thequantal content of transmitter release at the MOC-IHCsynapse. Postsynapticcholinergic currents, evoked by electrically stimulating the efferentfibers, were recorded in voltage-clamped (-90 mV) IHCs from acutely isolatedmouse organs of Corti. The quantal content of evoked release wassignificantly increased by 0.3 mM CGP55845 (60 ± 4% p< 0.001). The lack ofeffect of CGP55845 on spontaneous synaptic current amplitude indicates thatthe site of action of this drug is presynaptic. Our results suggest thatGABA might be exerting a negative feedback control on the release of ACh atthis synapse.