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European Archives of Oto-Rhino-Laryngology
Published in: European Archives of Oto-Rhino-Laryngology 10/2015

01-10-2015 | Otology

Decreased calcium-activated potassium channels by hypoxia causes abnormal firing in the spontaneous firing medial vestibular nuclei neurons

Authors: Hong Xie, Yu-qin Zhang, Xin-liang Pan, Shu-hui Wu, Xiang Chen, Jie Wang, Hua Liu, Xiao-zhong Qian, Zhi-guo Liu, Lie-Ju Liu

Published in: European Archives of Oto-Rhino-Laryngology | Issue 10/2015

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Abstract

Vertebrobasilar insufficiency (VBI) presents complex varied clinical symptoms, including vertigo and hearing loss. Little is known, however, about how Ca2+-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 Ca2+ 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.
Literature
1.
Erecinska M, Silver IA (2001) Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol 128:263–276CrossRefPubMed
2.
Schneider JI, Olshaker JS (2012) Vertigo, vertebrobasilar disease, and posterior circulation ischemic stroke. Emerg Med Clin N Am 30:681–693CrossRef
3.
Yamasoba T, Kikuchi S, Higo R (2001) Deafness associated with vertebrobasilar insufficiency. J Neurol Sci 187:69–75CrossRefPubMed
4.
Goldberg JM, Smith CE, Fernandez C (1984) Relation between discharge regularity and responses to externally applied galvanic currents in vestibular nerve afferents of the squirrel monkey. J Neurophysiol 51:1236–1256PubMed
5.
Cazin L, Precht W, Lannou J (1980) Firing characteristics of neurons mediating optokinetic responses to rat’s vestibular neurons. Pflugers Arch 386:221–230CrossRefPubMed
6.
Kim JS, Lee H (2009) Inner ear dysfunction due to vertebrobasilar ischemic stroke. Semin Neurol 29:534–540CrossRefPubMed
7.
Inoue S, Yamanaka T, Okamoto H, Hosoi H (2004) Effect of a glutamate blocker, ipenoxazone hydrochloride on the hypoxia-induced firing in the medial vestibular nucleus. Acta Otolaryngol Suppl. doi:10.​1080/​0365523041001768​9:​58-60
8.
Vassias I, Patko T, Vidal PP, de Waele C (2003) Modulation of the beta1-3 voltage-gated sodium channels in rat vestibular and facial nuclei after unilateral labyrinthectomy and facial nerve section: an in situ hybridization study. Brain Res Mol Brain Res 120:73–78CrossRefPubMed
9.
Ris L, Capron B, Nonclercq D et al (2003) Labyrinthectomy changes T-type calcium channels in vestibular neurones of the guinea pig. Neuroreport 14:1585–1589CrossRefPubMed
10.
de Waele C, Serafin M, Khateb A, Yabe T, Vidal PP, Muhlethaler M (1993) Medial vestibular nucleus in the guinea-pig: apamin-induced rhythmic burst firing—an in vitro and in vivo study. Exp Brain Res 95:213–222CrossRefPubMed
11.
Saito Y, Takazawa T, Ozawa S (2008) Relationship between afterhyperpolarization profiles and the regularity of spontaneous firings in rat medial vestibular nucleus neurons. Eur J Neurosci 28:288–298CrossRefPubMed
12.
van Welie I, du Lac S (2011) Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons. J Neurophysiol 105:1651–1659PubMedCentralCrossRefPubMed
13.
Nelson AB, Gittis AH, du Lac S (2005) Decreases in CaMKII activity trigger persistent potentiation of intrinsic excitability in spontaneously firing vestibular nucleus neurons. Neuron 46:623–631CrossRefPubMed
14.
Ghatta S, Nimmagadda D, Xu X, O’Rourke ST (2006) Large-conductance, calcium-activated potassium channels: structural and functional implications. Pharmacol Ther 110:103–116CrossRefPubMed
15.
Smith MR, Nelson AB, Du Lac S (2002) Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons. J Neurophysiol 87:2031–2042PubMed
16.
Womack MD, Hoang C, Khodakhah K (2009) Large conductance calcium-activated potassium channels affect both spontaneous firing and intracellular calcium concentration in cerebellar Purkinje neurons. Neuroscience 162:989–1000PubMedCentralCrossRefPubMed
17.
Faber ES, Sah P (2002) Physiological role of calcium-activated potassium currents in the rat lateral amygdala. J Neurosci 22:1618–1628PubMed
18.
Hendrich J, Alvarez P, Chen X, Levine JD (2012) GDNF induces mechanical hyperalgesia in muscle by reducing I(BK) in isolectin B4-positive nociceptors. Neuroscience 219:204–213PubMedCentralCrossRefPubMed
19.
Rodgers-Garlick CI, Hogg DW, Buck LT (2013) Oxygen-sensitive reduction in Ca(2)(+)-activated K(+) channel open probability in turtle cerebrocortex. Neuroscience 237:243–254CrossRefPubMed
20.
Zhang R, Sun H, Liao C et al (2012) Chronic hypoxia in cultured human podocytes inhibits BKCa channels by upregulating its beta4-subunit. Biochem Biophys Res Commun 420:505–510CrossRefPubMed
21.
Gavello D, Rojo-Ruiz J, Marcantoni A, Franchino C, Carbone E, Carabelli V (2012) Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study. PLoS One 7:e41530PubMedCentralCrossRefPubMed
22.
Marino M, Beny JL, Peyter AC, Diaceri G, Tolsa JF (2011) Perinatal hypoxia enhances cyclic adenosine monophosphate-mediated BKCa channel activation in adult murine pulmonary artery. J Cardiovasc Pharmacol 57:154–165CrossRefPubMed
23.
Veltkamp R, Domoki F, Bari F, Busija DW (1998) Potassium channel activators protect the N-methyl-D-aspartate-induced cerebral vascular dilation after combined hypoxia and ischemia in piglets. Stroke 29:837–842 (discussion 842–833)CrossRefPubMed
24.
Hughes JM, Riddle MA, Paffett ML, Gonzalez Bosc LV, Walker BR (2010) Novel role of endothelial BKCa channels in altered vasoreactivity following hypoxia. Am J Physiol Heart Circ Physiol 299:H1439–H1450PubMedCentralCrossRefPubMed
25.
Ye ZY, Li DP, Byun HS, Li L, Pan HL (2012) NKCC1 upregulation disrupts chloride homeostasis in the hypothalamus and increases neuronal activity-sympathetic drive in hypertension. J Neurosci 32:8560–8568PubMedCentralCrossRefPubMed
26.
Yoon KW, Covey DF, Rothman SM (1993) Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons. J Physiol 464:423–439PubMedCentralCrossRefPubMed
27.
Stone TW (1993) Neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev 45:309–379PubMed
28.
Fuchs AF, Kimm J (1975) Unit activity in vestibular nucleus of the alert monkey during horizontal angular acceleration and eye movement. J Neurophysiol 38:1140–1161PubMed
29.
Serafin M, de Waele C, Khateb A, Vidal PP, Muhlethaler M (1991) Medial vestibular nucleus in the guinea-pig. I. Intrinsic membrane properties in brainstem slices. Exp Brain Res 84:417–425CrossRefPubMed
30.
Serafin M, de Waele C, Khateb A, Vidal PP, Muhlethaler M (1991) Medial vestibular nucleus in the guinea-pig. II. Ionic basis of the intrinsic membrane properties in brainstem slices. Exp Brain Res 84:426–433CrossRefPubMed
31.
32.
Cao XH, Chen SR, Li L, Pan HL (2012) Nerve injury increases brain-derived neurotrophic factor levels to suppress BK channel activity in primary sensory neurons. J Neurochem 121:944–953PubMedCentralCrossRefPubMed
33.
Halliwell J (1990) K+ channels in the central nervous system. In: Cook NS (ed) Potassium channels, structure, classification, function and therapeutic potential. Wiley, New York, pp 348–381
34.
Hundahl CA, Luuk H, Ilmjarv S et al (2011) Neuroglobin-deficiency exacerbates Hif1A and c-FOS response, but does not affect neuronal survival during severe hypoxia in vivo. PLoS One 6:e28160PubMedCentralCrossRefPubMed
35.
Horn EM, Kramer JM, Waldrop TG (2000) Development of hypoxia-induced Fos expression in rat caudal hypothalamic neurons. Neuroscience 99:711–720CrossRefPubMed
36.
Teppema LJ, Veening JG, Kranenburg A, Dahan A, Berkenbosch A, Olievier C (1997) Expression of c-fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia. J Comp Neurol 388:169–190CrossRefPubMed
37.
Wahl AS, Buchthal B, Rode F et al (2009) Hypoxic/ischemic conditions induce expression of the putative pro-death gene Clca1 via activation of extrasynaptic N-methyl-D-aspartate receptors. Neuroscience 158:344–352CrossRefPubMed
38.
Huang L, Li Q, Li H et al (2009) Inhibition of intracellular Ca2+ release by a Rho-kinase inhibitor for the treatment of ischemic damage in primary cultured rat hippocampal neurons. Eur J Pharmacol 602:238–244CrossRefPubMed
39.
Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397CrossRefPubMed
40.
Gribkoff VK, Starrett JE Jr, Dworetzky SI et al (2001) Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels. Nat Med 7:471–477CrossRefPubMed
41.
Lukyanetz EA, Shkryl VM, Kravchuk OV, Kostyuk PG (2003) Action of hypoxia on different types of calcium channels in hippocampal neurons. Biochim Biophys Acta 1618:33–38CrossRefPubMed
42.
Mironov SL, Richter DW (2000) Hypoxic modulation of L-type Ca(2+) channels in inspiratory brainstem neurones: intracellular signalling pathways and metabotropic glutamate receptors. Brain Res 869:166–177CrossRefPubMed
43.
44.
Runden-Pran E, Haug FM, Storm JF, Ottersen OP (2002) BK channel activity determines the extent of cell degeneration after oxygen and glucose deprivation: a study in organotypical hippocampal slice cultures. Neuroscience 112:277–288CrossRefPubMed
45.
Muller M, Somjen GG (2000) Na(+) and K(+) concentrations, extra- and intracellular voltages, and the effect of TTX in hypoxic rat hippocampal slices. J Neurophysiol 83:735–745PubMed
46.
Schiff SJ, Somjen GG (1985) Hyperexcitability following moderate hypoxia in hippocampal tissue slices. Brain Res 337:337–340CrossRefPubMed
47.
Huang H, Gao TM, Gong L, Zhuang Z, Li X (2001) Potassium channel blocker TEA prevents CA1 hippocampal injury following transient forebrain ischemia in adult rats. Neurosci Lett 305:83–86CrossRefPubMed
48.
Wei L, Yu SP, Gottron F, Snider BJ, Zipfel GJ, Choi DW (2003) Potassium channel blockers attenuate hypoxia- and ischemia-induced neuronal death in vitro and in vivo. Stroke 34:1281–1286CrossRefPubMed
49.
Yao H, Gao Q, Xia Q (2010) The role of mitochondrial K+channels in the cardioprotection of puerarin against hypoxia/reoxygenation injury in rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi 26:459–462PubMed
50.
Dal-Cim T, Martins WC, Santos AR, Tasca CI (2011) Guanosine is neuroprotective against oxygen/glucose deprivation in hippocampal slices via large conductance Ca(2+)-activated K+ channels, phosphatidilinositol-3 kinase/protein kinase B pathway activation and glutamate uptake. Neuroscience 183:212–220CrossRefPubMed
51.
Levin SG, Godukhin OV (2009) Role of Ca(2+)-activated potassium channels with high-conductivity in hypoxic preconditioning and posthypoxic hyperexcitability in CA1 hippocampal neurons in vitro. Zh Vyssh Nerv Deiat Im I P Pavlova 59:622–629PubMed
Metadata
Title
Decreased calcium-activated potassium channels by hypoxia causes abnormal firing in the spontaneous firing medial vestibular nuclei neurons
Authors
Hong Xie
Yu-qin Zhang
Xin-liang Pan
Shu-hui Wu
Xiang Chen
Jie Wang
Hua Liu
Xiao-zhong Qian
Zhi-guo Liu
Lie-Ju Liu
Publication date
01-10-2015
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Oto-Rhino-Laryngology / Issue 10/2015
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-014-3158-4

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