INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
-“GABA regulates the release of ACh at the transient olivocochlear efferent-inner hair cell synapse through presynaptic GABAB receptors.
Autor/es:
WEDEMEYER , C; ZORRILLA DE SAN MARTÍN, J.; TORBIDONI, AV; BETTLER; B; ELGOYHEN, A.B; KATZ, E.
Lugar:
Lisboa
Reunión:
Congreso; Inner Ear Biology Workshop; 2011
Institución organizadora:
Inner Ear Biology (IEB)
Resumen:
Before  the  onset  of  hearing,  inner  hair  cells  (IHCs)  of  the  mammalian  cochlea  are  transiently innervated by medial olivocohlear (MOC) efferent fibers. Although acetylcholine (ACh) is the main neurotransmitter, γ-aminobutiric acid (GABA) is also present at MOC synaptic terminals. To study the  role  of  the  Gabaergic  system  at  the  MOC-IHC  synapse,  we  evaluated  the  effects  of compounds  selective  for  GABAB  receptors  on  the  quantal  content  of  transmitter  release. Postsynaptic  currents  evoked  by  electrically  stimulating  the  efferent  fibers  were  recorded  in voltage-clamped IHCs from isolated mouse organs of Corti at postnatal days 9 to 11. The quantal content  of  evoked  release  was  increased  by  the  GABAB  antagonist  CGP35348  (65±19%,  n=6 p<0.05)  and  decreased  by  the  agonist  baclofen  (43.07±8%,  n=8,  p<0.001).  These  results, together  with  the  lack  of  effect  of these  two  drugs  on  spontaneous  synaptic  current  amplitude, suggest  that  GABA  exerts  a  negative  control  on  synaptic  transmission  through  presynaptic GABAB  receptors.  To  confirm  this  hypothesis,  we  studied  the  effects  of  baclofen  on  GABAB knock-out (KO) mice. Functional GABAB receptors are formed by the GABAB2 subunit with either the  GABAB1a  or  the  GABAB1b  subunit.  We  compared  the  effects  of  baclofen  in  GABAB1a-1b, GABAB1a  and GABAB1b KO mice. Application of 1uM baclofen, caused a significant reduction in the quantal content of evoked release in both wild-type (32.3±6.9 %, n=5, p<0.05) and GABAB1b KO mice (26.7±7.7 %, n=4, p<0.05). However, baclofen did not affect this parameter in GABAB1a-1b  (p>0.05, n=3) or GABAB1a  KO mice (p>0.05, n=3). Our results show that ACh release at the MOC-IHC synapse is negatively regulated by GABA acting on presynaptic GABAB1a  receptors.