Voltage-gated Ca2+ channels (VGCC) that mediate Acetylcholine (ACh) release at the transient efferent-inner hair cell (IHC) synapse during neonatal development.

KEARNEY, GI; ZORRILLA DE SAN MARTÍN, J.; WEDEMEYER , C; ELGOYHEN, A.B; KATZ, E.

Huerta Grande - Córdoba

Congreso; XXVIII Congreso de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2013

Sociedad Argentina de Neurosciencias

During neonatal development IHCs are transiently innervated by medial olivocochlear (MOC) fibers. At postnatal days (P) 9-11, ACh release is supported by both P/Q and N-type VGCC and negatively regulated by L-type VGCC, coupled to the activation of BK channels. We previously reported that at P5-7, P/Q- but not N-type VGCC partially support ACh release and that BK channels reduce the quantal content (m) of evoked release. Our goal is now to determine which other type/s of VGCCs mediate ACh release at this stage and whether L-type VGCCs are coupled to the activation of BK channels. Postsynaptic responses were monitored in whole-cell voltage-clamped IHCs while electrically stimulating the efferent fibers in P5-7 mouse cochleas. Surpirsingly, both the L-type VGCC antagonist (Nifedipine) and the agonist (Bay-K) enhanced m (%increment = 161±21, 3 uM Nife; 294±26, 10 uM Bay-K). This suggests that L-type VGCC might be both supporting release and activating BK channels. However, occlusion experiments show that Bay-K has no effect on m after blocking BK channels with iberiotoxin (Ibtx) (m = 0.95, control; 2.7, Ibtx; 2.8, Ibtx + Bay-K). Moreover, Ibtx has no effect on m after incubation with L-type VGCC modulators (m = 0.8 ± 0.2 control; 2.49 ± 0.03 Nife; 2.9 ± 0.05 Nife+Ibtx; m = 0.7 ± 0.19 control; 1.9 ± 0.31 Bay-K; 2.1 ± 0.57 Bay-K+Ibtx). This shows that L-type VGCCs are coupled to BK channel activation. The paradoxical effect of Bay-K at this stage is being investigated.