INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Calcium Channels That Support Acetylcholine Release At the Transient
Autor/es:
ZORRILLA DE SAN MARTIN, J.; WEDEMEYER , C; FUCHS, P.; ELGOYHEN, A.B; KATZ, E.
Lugar:
New London, NH, Estados Unidos
Reunión:
Conferencia; Gordon Conference on Auditory Systems; 2008
Institución organizadora:
Gordon Research Conferences
Resumen:
Before the onset of hearing, inner hair cells (IHC) of the mammalian cochlea are transiently
innervated by efferent fibers from the medial olivocochlear system. This synapse is
cholinergic, inhibitory and mediated by the á9á10 nicotinic receptor. During postnatal
development, IHC undergo dramatic changes in cholinergic sensitivity, pattern of
innervation and expression of postsynaptic proteins. In developing synapses, synaptic
modifications likely take place concurrently in both postsynaptic cells and presynaptic
terminals. In mammals, fast synaptic transmission is mediated by multiple types of voltagegated
Ca2+ channels (VGCCs), including N-, P/Q- and R-type. In this work, we evaluated
the type/s of Ca2+ channels coupled to ACh release at the transient efferent-IHC synapse.
We used an acutely isolated cochlear preparation from mice and studied the effects of
different Ca2+ channel blockers on the quantal content (m) of transmitter release and on the
amplitude of spontaneous synaptic currents (sIPSCs). Postsynaptic cholinergic currents
(eIPSCs) in IHCs, voltage-clamped at -90 mV, were evoked by electrically stimulating the
efferent fibers. Both w-conotoxinGVIA (300 nM), an N-type VGCC blocker and w-
AgatoxinIVA (200 nM), a P/Q-type VGCC blocker, significantly reduced m to 44.5 ± 6.8
% (n=5) and 55.8 ± 15.1 % (n=4) of control, respectively. When both toxins were applied
together, ACh release was reduced to 3.9 ± 0.6 of control (n=4). Conversely, m increased to
209 ± 29 % (n=5) of control in the presence of the L-type channel antagonist, Nifedipine (3
ìM). ACh release was also significantly enhanced (244 ± 41% of control, n= 7) by
Iberiotoxin, a specific, BK channel antagonist. Preliminary results indicate that the block of
BK channels occludes the enhancing effect of Nifedipine. None of the toxins tested affected
the amplitude of sIPSCs, indicating that their site of action is only presynaptic. Our results
suggest that the entry of Ca2+ through both N and P/Q-type VGCC support ACh release at
this synapse, whereas the entry of Ca2+ through L-type channels might be activatating BK
channels, which contribute to the repolarization of the presynaptic membrane, thus
reducing the amount of ACh released per nerve impulse.