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Ca2+ and Ca2+-Activated K+ Channels That Support and Modulate Transmitter Release at the Olivocochlear Efferent-Inner Hair Cell Synapse

de San Martin, JZ; Pyott, S; Ballestero, J; Katz, E; (2010) Ca2+ and Ca2+-Activated K+ Channels That Support and Modulate Transmitter Release at the Olivocochlear Efferent-Inner Hair Cell Synapse. JOURNAL OF NEUROSCIENCE , 30 (36) 12157 - 12167. 10.1523/JNEUROSCI.2541-10.2010. Green open access

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Abstract

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 Ca2+-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 which are known to curtail the duration of the terminal action potential in several types of neurons.

Type: Article
Title: Ca2+ and Ca2+-Activated K+ Channels That Support and Modulate Transmitter Release at the Olivocochlear Efferent-Inner Hair Cell Synapse
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.2541-10.2010
Language: English
Additional information: This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The license allows you to copy, distribute, and transmit the work, as well as adapting it. However, you must attribute the work to the author (but not in any way that suggests that they endorse you or your use of the work), and cannot use the work for commercial purposes without prior permission of the author. If you alter or build upon this work, you can distribute the resulting work only under the same or similar license to this one. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1343799
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