Purinergic modulation of acetylcholine release at the efferent-inner hair cell synapse in the developing inner ear

FACUNDO ALVAREZ HEDUAN; ELEONORA KATZ; JUAN GOUTMAN; ANA B. ELGOYHEN

Huerta Grande, Córdoba

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2013

Sociedad Argentina de Investigación en Neurociencia

Before the onset of hearing (postnatal day (P) 12 in mice) inner hair cells (IHCs) are transiently innervated by medial olivocochlear (MOC) efferent fibers. Acetylcholine released by these fibers activates 910 nicotinic receptors coupled to SK2 calcium-activated potassium channels, leading to inhibitory post synaptic currents (IPSCs). During this developmental period, IHCs fire spontaneous sensory-independent action potentials that are required for normal development of the auditory pathway. Recent studies suggest that this spontaneous activity is driven and/or modulated by ATP released from cochlear supporting cells. Recently, we showed that ATP (100M) decreases the quantal content (m) of evoked release (50 %) in mouse IHCs at P9-P12, suggesting a pre-synaptic inhibitory modulating mechanism. In this work we investigated which ATP receptor subtypes are responsible for this modulation. IPSCs were evoked by electrically stimulating MOC fibers in the presence of different ATP receptor agonists and antagonists. Suramin (150 M), a non-specific P2 antagonist, abolished the effect of ATP. PPADS (50 M), an antagonist with a preferential effect on P2X receptors and TNP-ATP (10 M), a specific P2X antagonist, did not modify ATP-induced inhibition. Furthermore, -MeATP (50 M), a specific P2X agonist, had no effect on m. Our results suggest that P2X receptors would not be involved in the modulation the MOC-IHC synapse, leading to a principal roll of P2Y receptors.