title: The coupling of acetylcholine-induced BK channel and calcium channel in guinea pig saccular type II vestibular hair cells.
abstract: Molecular biological studies and electrophysiological data have demonstrated that acetylcholine (ACh) is the principal cochlear and vestibular efferent neurotransmitter among mammalians. However, the functional roles of ACh in type II vestibular hair cells (VHCs II) among mammalians are still unclear, with the exception of the well-known alpha9-containing nicotinic ACh receptor (alpha9-containing nAChR)-activated small conductance, calcium-dependent potassium current (SK) in cochlear hair cells and frog saccular hair cells. The activation of SK current was necessary for the calcium influx through the alpha9-containing nAChR. Recently, we have demonstrated that ACh-induced big conductance, calcium-dependent potassium current (BK) was present in VHCs II of the vestibular end-organ of guinea pig. In this study, the nature of calcium influx for the activation of ACh-induced BK current in saccular VHCs II of guinea pig was investigated. Following extracellular perfusion of ACh, saccular VHCs II displayed a sustained outward current, which was sensitive to iberiotoxin (IBTX). High concentration of apamin failed to inhibit the current amplitude of ACh-induced outward current. Intracellular application of Cs(+) completely abolished the current evoked by ACh. ACh-induced current was potently inhibited by nifedipine, nimodipine, Cd(2+) and Ni(2+), respectively. The inhibition potency of these four calcium channel antagonists was nimodipine>nifedipine>cadmium>nickel. The L-type Ca(2+) channels agonist, (-)-Bay-K 8644 mimicked the effect of ACh and activated an IBTX-sensitive current. In addition, partial VHCs II displayed a biphasic waveform. In conclusion, the present data showed that in the guinea pig saccular VHCs II, ACh-induced BK channel was coupled with the calcium channel, but not the receptor. The perfusion of ACh will drive the opening of calcium channels; the influx of calcium ions will then activate the BK current.
authors.affiliation: Department of Otolaryngology, Union Hospital of Tongji Medical College, Hua-Zhong University of Science and Technology, Wu Han, 430022, People's Republic of China. wjkong889@yahoo.com
authors.forename: Wei-Jia
authors.initials: WJ
authors.lastname: Kong
authors.forename: Chang-Kai
authors.initials: CK
authors.lastname: Guo
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhang
authors.forename: Xiong
authors.initials: X
authors.lastname: Chen
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Guan-Qiao
authors.initials: GQ
authors.lastname: Li
authors.forename: Zhi-Wang
authors.initials: ZW
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: Van Cauwenberge
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D004525:Efferent Pathways / Q000378:metabolism*; D006168:Guinea Pigs; D018069:Hair Cells, Vestibular / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D012444:Saccule and Utricle / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D002586:Cesium; D001030:Apamin; C064719:iberiotoxin; D000109:Acetylcholine; D002118:Calcium