Acetylcholine release at the transient olivocochlear efferent-inner hair cell synapse is supported by both N- and P/Q-type voltage-gated calcium channels.

JAVIER ZORRILLA DE SAN MARTÍN; CAROLINA WEDEMEYER; PAUL FUCHS; ANA BELÉN ELGOYHEN; ELEONORA KATZ

Colby-Sawyer College New London, NH, USA

Congreso; Gordon Conference on Auditory Systems; 2008

<!-- /* 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;} --> Before the onset of hearing, inner hair cells (IHC) of the mammalian cochleaare transiently innervated by medial olivocohlear efferent fibers. Thissynapse is cholinergic, inhibitory and mediated by the receptor. Duringpostnatal development, IHC undergo dramatic changes in cholinergicsensitivity, pattern of innervation and expression of key postsynapticproteins. In developing synapses, synaptic modifications likely take placeconcurrently in both postsynaptic cells and presynaptic terminals. Inmammals, fast synaptic transmission at both central and peripheral synapsesis mediated by multiple types of voltage-gated Ca2+ channels (VGCCs),including N-type (Cav2.2), P/Q (Cav2.1) type and R-type (Cav2.3). So far,nothing is known concerning the VGCCs that support ACh release at theefferent-IHC synapse. Therefore, in this work we evaluated the type/s ofCa2+ channels coupled to ACh release at this synapse before the onset ofhearing. We used the acutely isolated cochlear preparation from mice andevaluated the effects of different Ca2+ channel blockers on the quantalcontent (m) of transmitter release and on the amplitude of spontaneoussynaptic currents. Postsynaptic cholinergic currents in IHCs,voltage-clamped at -90 mV, were evoked by electrically stimulating theefferent fibers. Both (200 nM), a P/Q-type VGCC blocker, significantlyreduced m (49 ± 17%, n=5 and 52 ± 8%, n=4, respectively). When both toxinswere applied together, ACh release was reduced by 96% (n=1). Neither of thetoxins affected the amplitude of spontaneous synaptic currents (n=2-3),indicating that their site of action is only presynaptic. Our resultssuggest that both N and P/Q-type VGCCs support ACh release at the transientefferent-IHC synapse.Supported by a grant from NOHR to EK