ACh Release at the Efferent-IHC Synapse is Modulated by Presynaptic GABAB Receptors

WEDEMEYER C; BALLESTERO J; ZORRILA DE SAN MARTIN J; ELGOYHEN AB; KATZ E

Anaheim, California, USA

Congreso; 33rd Midwinter Meeting of the Association for Research in Otolaryngology; 2010

ARO

<!-- /* 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"; mso-ansi-language:ES-AR;} @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;} --> During development, before the onset of hearing, inner hair cells (IHCs) of the mammalian cochlea are transiently innervated by medial olivocochlear (MOC) efferent fibers. Although acetylcholine (ACh) is the main neurotransmitter released at this synapse, there is evidence showing that g-aminobutiric acid (GABA) is also present at MOC synaptic terminals. The possibility that synaptically released GABA could modulate the cholinergic input at MOC-synapses by acting on presynaptic GABAB receptors has not been investigated yet. We have previously shown that transmitter release at this synapse is supported by both P/Q and N-type calcium channels (San Martin et al., ARO Abstracts 2008).  In this work, we evaluated the effects of compounds selective for GABAB receptors on the quantal content of transmitter release at the MOC-IHC synapse. Postsynaptic currents, evoked by electrically stimulating the efferent fibers, were recorded in voltage-clamped (-90 mV) IHCs from acutely isolated mouse organs of Corti at postnatal days 9 to 11. The quantal content of evoked release was significantly increased by the GABAB antagonist CGP35348 at 1mM (55 ± 19 %,  p less than 0.05) and significantly decreased by 1mM of the agonist baclofen (68 ± 8 %, p less than 0.001). Our results suggest that GABA might be exerting a negative feedback control on the release of ACh through presynaptic GABAB receptors at MOC terminals. We are currently evaluating whether this effect is through the modulation of either P/Q and/or N-type calcium channels.