title: Decreased calcium-activated potassium channels by hypoxia causes abnormal firing in the spontaneous firing medial vestibular nuclei neurons.
abstract: Vertebrobasilar insufficiency (VBI) presents complex varied clinical symptoms, including vertigo and hearing loss. Little is known, however, about how Ca(2+)-activated K(+) channel attributes to the medial vestibular nucleus (MVN) neural activity in VBI. To address this issue, we performed whole-cell patch clamp and quantitative polymerase chain reaction (qPCR) to examine the effects of hypoxia on neural activity and the changes of the large conductance Ca(2+) activated K(+) channels (BKCa channels) in the MVN neurons in brain slices of male C57BL/6 mice. Brief hypoxic stimuli of the brain slices containing MVN were administrated by switching the normoxic artificial cerebrospinal fluid (ACSF) equilibrated with 21% O2/5% CO2 to hypoxic ACSF equilibrated with 5% O2/5% CO2 (balance N2). 3-min hypoxia caused a depolarization in the resting membrane potential (RM) in 8/11 non-spontaneous firing MVN neurons. 60/72 spontaneous firing MVN neurons showed a dramatic increase in firing frequency and a depolarization in the RM following brief hypoxia. The amplitude of the afterhyperpolarization (AHPA) was significantly decreased in both type A and type B spontaneous firing MVN neurons. Hypoxia-induced firing response was alleviated by pretreatment with NS1619, a selective BKCa activator. Furthermore, brief hypoxia caused a decrease in the amplitude of iberiotoxin-sensitive outward currents and mRNA level of BKCa in MVN neurons. These results suggest that BKCa channels protect against abnormal MVN neuronal activity induced by hypoxia, and might be a key target for treatment of vertigo and hearing loss in VBI.
authors.affiliation: Jingzhou Central Hospital, Jingzhou, 434020, People's Republic of China, xiehongjz@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Yu-qin
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Xin-liang
authors.initials: XL
authors.lastname: Pan
authors.forename: Shu-hui
authors.initials: SH
authors.lastname: Wu
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Xiao-zhong
authors.initials: XZ
authors.lastname: Qian
authors.forename: Zhi-guo
authors.initials: ZG
authors.lastname: Liu
authors.forename: Lie-Ju
authors.initials: LJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D015837:Vestibular Diseases / Q000378:metabolism / Q000503:physiopathology*; D014726:Vestibular Nuclei / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D024681:Potassium Channels, Calcium-Activated