Ca2+and Ca2+-activated K+ channels that support and modulate transmitter release at the olivocochlear efferent-inner hair cell synapse

Authors
De San Martín, J.Z.; Pyott, S.; <div class="autor_fcen" id="559">Ballestero, J.</div>; <div class="autor_fcen" id="4549">Katz, E.</div>
Publication Year
2010
Language
English
Format
article
Status
Published version
Description
In the mammalian auditory system, the synapse between efferent olivocochlear (OC) neurons and sensory cochlear hair cells is cholinergic, fast, and inhibitory. This efferent synapse is mediated by the nicotinic α9α10 receptor coupled to the activation of SK2 Ca 2+-activated K+ channels that hyperpolarize the cell. So far, the ion channels that support and/or modulate neurotransmitter release from the OC terminals remain unknown. To identify these channels, we used an isolated mouse cochlear preparation and monitored transmitter release from the efferent synaptic terminals in inner hair cells (IHCs) voltage clamped in the whole-cell recording configuration. Acetylcholine (ACh) release was evoked by electrically stimulating the efferent fibers that make axosomatic contacts with IHCs before the onset of hearing. Using the specific antagonists for P/Q- and N-type voltage-gated calcium channels (VGCCs), ω-agatoxin IVA and ω-conotoxin GVIA, respectively, we show that Ca2+ entering through both types of VGCCs support the release process at this synapse. Interestingly, we found that Ca2+ entering through the dihydropiridine-sensitive L-type VGCCs exerts a negative control on transmitter release. Moreover, using immunostaining techniques combined with electrophysiology and pharmacology, we show that BK Ca2+-activated K+ channels are transiently expressed at the OC efferent terminals contacting IHCs and that their activity modulates the release process at this synapse. The effects of dihydropiridines combined with iberiotoxin, a specific BK channel antagonist, strongly suggest that L-type VGCCs negatively regulate the release of ACh by fueling BK channels that are known to curtail the duration of the terminal action potential in several types of neurons. Copyright © 2010 the authors.
Fil:Ballestero, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Source
J. Neurosci. 2010;30(36):12157-12167
Subject
acetylcholine
calcium activated potassium channel
calcium channel L type
calcium channel N type
calcium channel P type
calcium channel Q type
calcium ion
calretinin
cell marker
iberiotoxin
nifedipine
nitrendipine
omega agatoxin IVA
omega conotoxin GVIA
synapsin
voltage gated calcium channel
acetylcholine release
animal cell
animal tissue
article
cochlear nerve
controlled study
Corti organ
efferent nerve
electrostimulation
female
fluorescence microscopy
hair cell
immunohistochemistry
inhibitory postsynaptic potential
isolated organ
male
mouse
nonhuman
pharmacological blocking
priority journal
protein expression
protein function
protein localization
synapse
voltage clamp
whole cell
Acetylcholine
Animals
Animals, Newborn
Biophysics
Calcium
Calcium Channel Blockers
Dose-Response Relationship, Drug
Electric Stimulation
Female
Hair Cells, Auditory, Inner
Inhibitory Postsynaptic Potentials
Male
Mice
Mice, Inbred BALB C
Olivary Nucleus
Organ of Corti
Patch-Clamp Techniques
Peptides
Potassium Channel Blockers
Potassium Channels, Calcium-Activated
Synapses
Synaptic Transmission
Access level
Open access
License
http://creativecommons.org/licenses/by/2.5/ar
Repository
Biblioteca Digital (UBA-FCEN)
Institution
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
OAI Identifier
snrd:HASH01b6ab397fe2b5bf609b22e8