The expression of muscarinc acetylcholine receptors on the avian vestibular hair cells and the modulation effects on KIR2.1

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Title: The expression of muscarinc acetylcholine receptors on the avian vestibular hair cells and the modulation effects on KIR2.1
Author: Gang Q Li
Abstract: The major neurotransmitter released from the vestibular efferent terminals onto hair cells is acetylcholine (ACh ) . Two types of acetylcholine receptors (AChRs ) have been suggested to be located on hair cells (HCs ) . They were nicotinic receptors (nAChRs ) and muscarinic receptors (mAChRs ) . Even though pioneering physiological and pharmacological studies have shown evidence of mAChR located on the HCs , the protein expression and the role of muscarinic acetylcholine receptor (mAChR ) in HCs have not been carefully studied . Our preliminary data indicated that the activation of mAChRs on pigeon vestibular type II HCs produced an inhibitory effect on an inward rectifier potassium channel , Kir2 .1 . Using immunohistochemical , immunocytochemical , and Western blot techniques , we demonstrated for the first time , the expression and co -expression of mAChR subtypes M1 -M5 on the peripheral vestibular structures , including hair cells , supporting cells , ganglion , and other neural elements . To better understand the modulation effects of mAChR activation on Kir2 .1 channels , the heterologous expression system (HES ) was used to express a single mAChR subtype and Kir2 .1 . The expression plasmids for M3 or M5 mAChR subtype were co -transfected with pKir2 .1 into the mammalian cell line tsA201 cells and electrophysiological studies including whole cell voltage clamp and current clamp were performed . Muscarinic receptor agonist (CCh ) application to the tsA201 cells transfected with M3 &pKir2 .1 or M5 &pKir2 .1 exhibited concentration - and time - dependent facilitatory and /or inhibitory effects on the pKir2 .1 channels . These effects depolarized or hyperpolarized the cell membrane potential , respectively . Further electrophysiological experiments were performed on native isolated \r \nvii \r \navian (pigeon ) vestibular HCs . Whole cell patch clamp on both type I and type II HCs indicated that mAChR activation decreased both inward and outward current (type I & type II ) which consequently produced hyperpolarization (type II ) and depolarization (type I & type II ) . We also noticed that nAChR activation increased the outward current (type I & type II ) and inward current (type II ) which hyperpolarized the membrane potential (type I & type II ) or depolarized the membrane potential (type II ) . In conclusion , mAChR played a role in the control of membrane potentials by modulating the ionic channels . The mechanism of mAChR induced effects is still unknown .
URI: http : / /hdl .handle .net /2152 .3 /286
Date: 2008-11-26

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The expression of muscarinc acetylcholine receptors on the avian vestibular hair cells and the modulation effects on KIR2.1. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /286 .

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