Ca2+and Ca2+-activated K+ channels that support and modulate transmitter release at the olivocochlear efferent-inner hair cell synapse
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 hyperpol...
| Autores: | , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2010 |
| País: | Argentina |
| Recursos: | Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
| Repositorio: | Biblioteca Digital (UBA-FCEN) |
| Idioma: | inglés |
| OAI Identifier: | paperaa:paper_02706474_v30_n36_p12157_DeSanMartin |
| Acesso em linha: | http://hdl.handle.net/20.500.12110/paper_02706474_v30_n36_p12157_DeSanMartin |
| Access Level: | acceso abierto |
| Palavra-chave: | 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 calcium calcium channel blocking agent peptide potassium channel blocking agent 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 animal antagonists and inhibitors Bagg albino mouse biophysics cytology dose response drug effects in vitro study metabolism newborn olivary nucleus patch clamp technique physiology procedures synaptic transmission 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 In Vitro Techniques |
| Resumo: | 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. |
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