<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article         dtd-version="1.4">
            <front>

                <journal-meta>
                                    <journal-id></journal-id>
            <journal-title-group>
                                                                                    <journal-title>Cell Membranes and Free Radical Research</journal-title>
            </journal-title-group>
                            <issn pub-type="ppub">1308-416X</issn>
                                                                                                        <publisher>
                    <publisher-name>Hücresel Sinir Bilimleri ve Oksidatif Stres Derneği</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id/>
                                                                                                                                                                                            <title-group>
                                                                                                                                                            <article-title>Functional expression of TRPA1 cation channels in vestibular type II hair cells</article-title>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                <name>
                                    <surname>Sparrer</surname>
                                    <given-names>İngo</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Duong Dinh</surname>
                                    <given-names>Thien An</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Jüngling</surname>
                                    <given-names>Eberhard</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Westhofen</surname>
                                    <given-names>Martin</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Lückhoff</surname>
                                    <given-names>Andreas</given-names>
                                </name>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20130814">
                    <day>08</day>
                    <month>14</month>
                    <year>2013</year>
                </pub-date>
                                        <volume>3</volume>
                                        <issue>1</issue>
                                        <fpage>139</fpage>
                                        <lpage>144</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20110722">
                        <day>07</day>
                        <month>22</month>
                        <year>2011</year>
                    </date>
                                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 2008, Cell Membranes and Free Radical Research</copyright-statement>
                    <copyright-year>2008</copyright-year>
                    <copyright-holder>Cell Membranes and Free Radical Research</copyright-holder>
                </permissions>
            
                                                                                                                        <abstract><p>Although the expression of TRPA1 proteins has been demonstrated in hair cells of the inner ear, the role of this Ca2+-permeable cation channel is unclear because TRPA1 knock-out mice have normal transduction currents in hair cells and do not show hearing impairment or vestibular problems. To test whether TRPA1 expression leads to the formation of intact ion channels in the plasma membrane of vestibular type II hair cells in the guinea pig, we measured whole-cell currents before and after stimulation with the specific agonists of TRPA1, allylisothiocyanate (AITC, 200 – 400 µM) and 3&#039;-carbamoylbiphenyl-3-yl cyclohexylcarbamate (URB597, 100 µM). AITC induced currents with the typical current-voltage relation of TRPA1, as found in heterologous expression models. Currents densities reached maxima 168 ± 22 pA/pF (n = 41) at a holding potential of +60 mV and -62 ± 16 pA/pF at -60 mV. Current kinetics were characterized by an initial increase in amplitude over about 60 s, a subsequent plateau, and a complete current decline after wash-out of the drug. Repeated stimulations were possible. In the presence of URB597, similar currents developed but showed rapid desensitization under ongoing stimulation. We conclude that there is functional expression of TRPA1 in vestibular hair cells, at a current density relatively small in comparison to voltage gated currents. Thus, TRPA1 currents may modulate the electrical responses of hair cells. This may be relevant as potential side effects of many drugs and substances known to be activators of the polymodal channels TRPA1.</p></abstract>
                                                            
            
                                                                                        <kwd-group>
                                                    <kwd>Ion channels</kwd>
                                                    <kwd>   cell biochemistry</kwd>
                                                    <kwd>   biophysics</kwd>
                                                    <kwd>   calcium signaling</kwd>
                                                    <kwd>   cellular function</kwd>
                                                    <kwd>   cellular physiology</kwd>
                                                    <kwd>   metabolism</kwd>
                                                    <kwd>   apoptosis</kwd>
                                                    <kwd>   lipid peroxidation</kwd>
                                                    <kwd>   nitric oxide synthase</kwd>
                                                    <kwd>   ageing</kwd>
                                                    <kwd>   antioxidants</kwd>
                                                    <kwd>   neuropathy</kwd>
                                            </kwd-group>
                            
                                                                                                                                                    </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ and Patapoutian A. 2004. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41: 849-857.</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">Bautista DM, Movahed P, Hinman A, Axelsson H E Sterner O, Högestätt ED, Julius D, Jordt SE and Zygmunt P. M. 2005. Pungent products from garlic activate the sensory ion channel TRPA1. Proc. Natl. Acad. Sci. U.S.A., 102: 12248-12252.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE. 2008. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest 118: 1899-1910.</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">Corey DP, García-Añoveros J, Holt JR, Kwan KY, Lin SY, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, Géléoc GS, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D, and Zhang DS. 2004. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432: 723-730.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">Duong Dinh TA, Jüngling E, Strotmann KH, Westhofen M, Lückhoff A. 2006. Ultrasonic bath depth control and regulation in single cell recordings. Pflugers Arch 452: 784-788.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">Düwel P, Haasler T, Jüngling E, Duong TA, Westhofen M, Lückhoff A. 2005. Effects of cinnarizine on calcium and pressure-dependent potassium currents in guinea pig vestibular hair cells. Naunyn Schmiedebergs Arch Pharmacol 371: 441-448.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">Fettiplace R. 2009. Defining features of the hair cell mechanoelectrical transducer channel. Pflügers Arch 458: 1115-1123.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">Fischer MJ, Leffler A, Niedermirtl F, Kistner K, Eberhardt M, Reeh PW, Nau C. 2010. The general anesthetic propofol excites nociceptors by activating TRPV1 and TRPA1 rather than GABAA receptors. J Biol Chem 285: 3478134792.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">Haasler T, Homann G, Duong Dinh TA, Jüngling E, Westhofen M, Lückhoff A. 2009.Pharmacological modulation of transmitter release by inhibition of pressure-dependent potassium currents in vestibular hair cells. Naunyn Schmiedebergs Arch Pharmacol 380: 531-538.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. 1981. Improved patchclamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391: 85-100.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">Hayashi K, Kobayashi R, Kitamura K, Goto F, Ogawa K, Matsumoto T. 2010. A novel model for prognosis of Meniere&#039;s disease using oxidative stress susceptibility of lymphoblastoid cell lines. Biosci Trends 4: 72-78.</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">Hill K, Schaefer M. 2008. Ultraviolet light and photosensitising agents activate TRPA1 via generation of oxidative stress. Cell Calcium 45: 155-164.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Högestätt ED, Meng ID and Julius D. 2004. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427: 260-265.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">Kim D, Cavanaugh EJ, Simkin D. 2008. Inhibition of transient receptor potential A1 channel by phosphatidylinositol-4,5-bisphosphate. Am J Physiol Cell Physiol 295: C92-99.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">Knox GW, McPherson A. 1997. Menière&#039;s disease: differential diagnosis and treatment. Am Fam Physician 55: 1185-1190, 1193-1194.</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ and Corey DP. 2006. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50: 177180.</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">Labbé D, Teranishi MA, Hess A, Bloch W, Michel O. 2005. Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea. Hear Res 202: 21-27.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">Lee SP, Buber MT, Yang Q, Cerne R, Cortés RY, Sprous DG, Bryant RW. Br J Pharmacol. 2008. Thymol and related alkyl phenols activate the hTRPA1 channel. 153: 1739-1749.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">Lin CY, Young YH. 2001. Effect of smoking on the treatment of vertigo. Otol Neurotol 22: 369-372.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">Macpherson LJ, Geierstanger BH, Viswanath V, Bandell M, Eid SR, Hwang S, Patapoutian A. 2005. The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr Biol 15: 929-934.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang S, Cravatt B, Corey DP and Patapoutian A. 2007. An ion channel essential for sensing chemical damage. J Neurosci 17;27: 11412-11415.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">Nagata K, Duggan A, Kumar G. and García-Añoveros J. 2005. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. J Neurosci 25: 4052-4061.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">Niforatos W, Zhang XF, Lake MR, Walter KA, Neelands T, Holzman TF, Scott VE, Faltynek CR, Moreland RB and Chen J. 2007. Activation of TRPA1 channels by the fatty acid amide hydrolase inhibitor 3’-carbamoylbiphenyl-3-yl cyclohexylcarbamate (URB597). Mol. Pharmacol 71: 1209-1216.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">Patil MJ, Jeske NA, Akopian AN. 2010. Transient receptor potential V1 regulates activation and modulation of transient receptor potential A1 by Ca2+. Neuroscience 171: 1109-1119.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">Ricci AJ, Cochran SL, Rennie KJ, Correia MJ. 1997. Vestibular type I and type II hair cells. 2: Morphometric comparisons of dissociated pigeon hair cells. J Vestib Res 7: 407-420.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">Takumida M, Ishibashi T, Hamamoto T, Hirakawa K, and Anniko, M. 2008. Expression of transient receptor potential channel melastin (TRPM) 1-8 and TRPA1 (ankyrin) in mouse inner ear. Acta Otolaryngol. 1-11.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, Thornton J, Carr MJ, Undem BJ. 2008. Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal. J Physiol 586: 3447-3459.</mixed-citation>
                    </ref>
                                    <ref id="ref28">
                        <label>28</label>
                        <mixed-citation publication-type="journal">Talavera K, Gees M, Karashima Y, Meseguer VM, Vanoirbeek JA, Damann N, Everaerts W, Benoit M, Janssens A, Vennekens R, Viana F, Nemery B, Nilius B, Voets T. 2009. Nicotine activates the chemosensory cation channel TRPA1. Nat. Neurosci 12: 1293-1299.</mixed-citation>
                    </ref>
                                    <ref id="ref29">
                        <label>29</label>
                        <mixed-citation publication-type="journal">Vilceanu D, Stucky CL. 2010. TRPA1 mediates mechanical currents in the plasma membrane of mouse sensory neurons. PLoS One 5: 12177.</mixed-citation>
                    </ref>
                                    <ref id="ref30">
                        <label>30</label>
                        <mixed-citation publication-type="journal">Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA. 2007. Direct activation of the ion channel TRPA1 by Ca2+. Nat. Neurosci 10: 277-279.</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
