<?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  article-type="research-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>Molecular expression and calcium signalling roles of  native TRP channels in vascular cells</article-title>
                                                                                                                                        </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                <name>
                                    <surname>Zholos</surname>
                                    <given-names>Alexander</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Melanaphy</surname>
                                    <given-names>Donal</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Borysova</surname>
                                    <given-names>Lyudmyla</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Kustov</surname>
                                    <given-names>Maksym</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Watson</surname>
                                    <given-names>Conall</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Johnson</surname>
                                    <given-names>Christopher</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Burdyga</surname>
                                    <given-names>Theodor</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>4</volume>
                                        <issue>2</issue>
                                        <fpage>195</fpage>
                                        <lpage>201</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20120601">
                        <day>06</day>
                        <month>01</month>
                        <year>2012</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>In the vasculature, multiple members of the TRP-superfamily of non-selective cation channels (NSCCs) are expressed. These channels mediate diverse non-voltage-gated Ca2+-entry pathways and functions, which involve both vascular myocytes and communicating endothelial cells. Here, we provide an overview of recent progress in this area of research and discuss several specific examples of the important roles of vascular TRP channels in calcium signalling and electrophysiological responses. We especially focus on the recently discovered signal transduction mechanisms involving formation of specific complexes between TRP proteins and other better studied proteins that regulate cell calcium homeostasis, such as voltage-gated calcium channels and ryanodine receptors. Finally, we provide an overview of the progress in our understanding of TRPM8, which is known as the principal neuronal cold receptor, expression, localisation and function in the vasculature. We conclude that this channel is likely involved in complex thermal behaviour of blood vessels, better understanding of which is relevant to hypothermic and cardiovascular surgery conditions, therefore further research in this area is needed.</p></abstract>
                                                                                    
            
                                                            <kwd-group>
                                                    <kwd>TRP channels</kwd>
                                                    <kwd>  Vascular smooth muscle</kwd>
                                                    <kwd>  Endothelium</kwd>
                                                    <kwd>  Calcium signalling</kwd>
                                                    <kwd>  Patch-clamp</kwd>
                                            </kwd-group>
                                                        
                                                                                                                                                    </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">Albert AP, Large WA. 2006. Signal transduction pathways and gating mechanisms of native TRP-like cation channels in vascular myocytes. J Physiol 570: 45-51.</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D. 2007. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448: 204-208.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">Baylie RL, Cheng H, Langton PD, James AF. 2010. Inhibition of the cardiac L-type calcium channel current by the TRPM8 agonist, (-)-menthol. J Physiol Pharmacol 61: 543-550.</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">Beech DJ. 2005. Emerging functions of 10 types of TRP cationic channel in vascular smooth muscle. Clin Exp Pharmacol P 32: 597-603.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">Beech DJ. 2007. Ion channel switching and activation in smooth-muscle cells of occlusive vascular diseases. Biochem Soc T 35: 890-894.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">Beech DJ, Muraki K, Flemming R. 2004. Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP, J Physiol 559: 685-706.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">Benham CD, Bolton TB, Byrne NG, Large WA. 1987. Action of externally applied adenosine triphosphate on single smooth muscle cells dispersed from rabbit ear artery. J Physiol 387: 473-488.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">Benham CD, Tsien RW. 1987. A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature 328: 275-278.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">Bodding M, Wissenbach U, Flockerzi V. 2007. Characterisation of TRPM8 as a pharmacophore receptor. Cell Calcium 42: 618-628.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">Byrne NG, Large WA. 1988a. Mechanism of action of alpha-adrenoceptor activation in single cells freshly dissociated from the rabbit portal vein. Brit J Pharmacol 94: 475-482.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">Byrne NG, Large WA. 1988b. Membrane ionic mechanisms activated by noradrenaline in cells isolated from the rabbit portal vein. J Physiol 404: 557-573.</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">Clapham DE, Julius D, Montell C, Schultz G. 2005. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev 57: 427-450.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">Earley S, Gonzales AL, Crnich R. 2009b. Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+  channels. Circ Res 104: 987-994.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">Earley S, Heppner TJ, Nelson MT, Brayden JE. 2005. TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels. Circ Res 97: 1270-1279.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">Earley S, Pauyo T, Drapp R, Tavares MJ, Liedtke W, Brayden J. 2009a. TRPV4- dependent dilation of peripheral resistance arteries influences arterial pressure. Am J Physiol-Heart C 297: H1096-H1102.</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">Firth AL, Remillard CV, Yuan,JX. 2007. TRP channels in hypertension. Biochim Biophys Acta 1772: 895-906.</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">Garland CJ, Plane F, Kemp BK, Cocks TM. 1995. Endothelium-dependent hyperpolarization: a role in the control of vascular tone. Trends Pharmacol Sci 16: 23-30.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">Gees M, Colsoul B, Nilius B. 2010. The role of transient receptor potential cation channels in Ca2+ signalling. Cold Spring Harb Perspect biol 2: a003962.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">Gryglewski RJ, Botting RM, Vane JR. 1988. Mediators produced by the endothelial cell. Hypertension 12: 530-548.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">Gryglewski R, Moncada S, Palmer R. 1986. Bioassay of prostacyclin and endothelium-derived relaxing factor (EDRF) from porcine aortic endothelial cells. Brit J Pharmacol 87: 685-694.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">House SJ, Potier M, Bisaillon J, Singer HA, Trebak M. 2008. The non-excitable smooth muscle: calcium signaling and phenotypic switching during vascular disease. Pflug Arch Eur J Phy 456: 769-785.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. 1987. Endotheliumderived relaxing factor produced and released from artery and vein is nitric oxide. P Natl Acad Sci 84: 9265-9269.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">Inoue R, Jensen LJ, Shi J, Morita H, Nishida M, Honda A, Ito Y. 2006. Transient receptor potential channels in cardiovascular function and disease. Circ Res 99: 119-131.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">Inoue R, Jian Z, Kawarabayashi Y. 2009. Mechanosensitive TRP channels in cardiovascular pathophysiology. Pharmacol Therapeut 123: 371-85.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">Inoue R, Okada T, Onoue H, Hara Y, Shimizu S, Naitoh S, Ito Y, Mori Y. 2001. The transient receptor potential protein homologue TRP6 is the essential component of vascular Į1-adrenoceptor-activated Ca2+-permeable cation channel. Circ Res 88: 325-332.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">Jenkins CM, Han X, Mancuso DJ, Gross RW. 2002. Identification of calciumindependent phospholipase A2 (iPLA2 )ȕ, and not iPLA2 Ȗ, as the mediator of arginine vasopressin-induced arachidonic acid release in A-10 smooth muscle cells. Enantioselective mechanism-based discrimination of mammalian iPLA2s. J Biol Chem 277: 32807-32814.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">Johnson CD, Melanaphy D, Purse A, Stokesberry SA, Dickson P, Zholos AV. 2009. Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone. Am J Physiol-Heart C 296: H1868-H1877.</mixed-citation>
                    </ref>
                                    <ref id="ref28">
                        <label>28</label>
                        <mixed-citation publication-type="journal">Liu B, Peel SE, Fox J, Hall IP. 2010. Reverse mode Na+ /Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulation. Respir Res 11: 168-179.</mixed-citation>
                    </ref>
                                    <ref id="ref29">
                        <label>29</label>
                        <mixed-citation publication-type="journal">McKemy DD, Neuhausser WM, Julius D. 2002. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416: 52-58.</mixed-citation>
                    </ref>
                                    <ref id="ref30">
                        <label>30</label>
                        <mixed-citation publication-type="journal">Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX. 2002. A unified nomenclature for the superfamily of TRP cation channels. Mol Cell 9: 229231.</mixed-citation>
                    </ref>
                                    <ref id="ref31">
                        <label>31</label>
                        <mixed-citation publication-type="journal">Nakashima M, Mombouli JV, Taylor AA, Vanhoutte PM. 1993. Endotheliumdependent hyperpolarization caused by bradykinin in human coronary arteries. J Clin Invest 92: 2867-2871.</mixed-citation>
                    </ref>
                                    <ref id="ref32">
                        <label>32</label>
                        <mixed-citation publication-type="journal">Nelson M, Cheng H, Rubart M, Santana L, Bonev A, Knot H, Lederer W. 1995. Relaxation of arterial smooth muscle by calcium sparks. Science 270: 633- 637.</mixed-citation>
                    </ref>
                                    <ref id="ref33">
                        <label>33</label>
                        <mixed-citation publication-type="journal">Nilius B, Owsianik G, Voets T, Peters JA. 2007. Transient receptor potential cation channels in disease. Physiol Rev 87:165-217.</mixed-citation>
                    </ref>
                                    <ref id="ref34">
                        <label>34</label>
                        <mixed-citation publication-type="journal">Palmer RMJ, Rees DD, Ashton DS, Moncada S. 1988. L-arginine is the physiological precursor for the formation of nitric oxide in endotheliumdependent relaxation. Biochem Bioph Res Co 153: 1251-1256.</mixed-citation>
                    </ref>
                                    <ref id="ref35">
                        <label>35</label>
                        <mixed-citation publication-type="journal">Palmer R, Ferrige A, Moncada S. 1987. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524-526.</mixed-citation>
                    </ref>
                                    <ref id="ref36">
                        <label>36</label>
                        <mixed-citation publication-type="journal">Pedersen SF, Owsianik G, Nilius B. 2005. TRP channels: an overview. Cell Calcium 38: 233-252.</mixed-citation>
                    </ref>
                                    <ref id="ref37">
                        <label>37</label>
                        <mixed-citation publication-type="journal">Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A. 2002. A TRP channel that senses cold stimuli and menthol. Cell 108: 705-715.</mixed-citation>
                    </ref>
                                    <ref id="ref38">
                        <label>38</label>
                        <mixed-citation publication-type="journal">Poburko D, Liao CH, Lemos VS, Lin E, Maruyama Y, Cole WC, van Breemen C. 2007. Transient receptor potential channel 6-mediated, localized cytosolic [Na+ ] transients drive Na+ /Ca2+ exchanger-mediated Ca2+ entry in purinergically stimulated aorta smooth muscle cells. Circ Res 101: 1030- 1038.</mixed-citation>
                    </ref>
                                    <ref id="ref39">
                        <label>39</label>
                        <mixed-citation publication-type="journal">Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotliko! MI, Heppner TJ, HillEubanks, DC, Nelson NT. 2012. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science 336: 597-601.</mixed-citation>
                    </ref>
                                    <ref id="ref40">
                        <label>40</label>
                        <mixed-citation publication-type="journal">Takahashi N, Kuwaki T, Kiyonaka S, Numata T, Kozai D, Mizuno Y, Yamamoto S, Naito S, Knevels E, Carmeliet P, Oga T, Kaneko S, Suga S, Nokami T, Yoshida J, Mori Y. 2011. TRPA1 underlies a sensing mechanism for O2. Nat Chem Biol 7:701-711.</mixed-citation>
                    </ref>
                                    <ref id="ref41">
                        <label>41</label>
                        <mixed-citation publication-type="journal">Thebault S, Lemonnier L, Bidaux G, Flourakis M, Bavenco!e A, Gordienko D, Roudbaraki M, Delcourt P, Panchin Y, Shuba Y. 2005. Novel role of cold/ menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J Biol Chem 280: 39423-39435.</mixed-citation>
                    </ref>
                                    <ref id="ref42">
                        <label>42</label>
                        <mixed-citation publication-type="journal">Tsavaler L, Shapero MH, Morkowski S, Laus R. 2001. Trp-p8, a novel prostatespecific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 61: 3760-3769</mixed-citation>
                    </ref>
                                    <ref id="ref43">
                        <label>43</label>
                        <mixed-citation publication-type="journal">Tsuzuki K, Xing H, Ling J, Gu JG. 2004. Menthol-induced Ca2+ release from presynaptic Ca2+ stores potentiates sensory synaptic transmission. J Neurosci 24: 762-771.</mixed-citation>
                    </ref>
                                    <ref id="ref44">
                        <label>44</label>
                        <mixed-citation publication-type="journal">Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C. 1995. TRPC1, a human homolog of a Drosophila store-operated channel. P Natl Acad Sci USA 92: 9652-9656.</mixed-citation>
                    </ref>
                                    <ref id="ref45">
                        <label>45</label>
                        <mixed-citation publication-type="journal">Xu SZ, Beech DJ. 2001. TrpC1 is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells. Circ Res 88: 84-87.</mixed-citation>
                    </ref>
                                    <ref id="ref46">
                        <label>46</label>
                        <mixed-citation publication-type="journal">Wu LJ, Sweet TB, Clapham DE. 2010. International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol Rev 62: 381-404.</mixed-citation>
                    </ref>
                                    <ref id="ref47">
                        <label>47</label>
                        <mixed-citation publication-type="journal">Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. 1988. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411-415</mixed-citation>
                    </ref>
                                    <ref id="ref48">
                        <label>48</label>
                        <mixed-citation publication-type="journal">Yang XR, Lin MJ, McIntosh LS, Sham JS. 2006. Functional expression of transient receptor potential melastatin- and vanilloid-related channels in pulmonary arterial and aortic smooth muscle. Am J Physiol-Lung C 290: L1267-L1276.</mixed-citation>
                    </ref>
                                    <ref id="ref49">
                        <label>49</label>
                        <mixed-citation publication-type="journal">Yao X, Garland CJ. 2005. Recent developments in vascular endothelial cell transient receptor potential channels. Circ Res 97: 853-863.</mixed-citation>
                    </ref>
                                    <ref id="ref50">
                        <label>50</label>
                        <mixed-citation publication-type="journal">Zhang L, Barritt GJ. 2004. Evidence that TRPM8 is an androgen dependent Ca2+ channel required for the survival of prostate cancer cells. Cancer Res 64: 8365-8373.</mixed-citation>
                    </ref>
                                    <ref id="ref51">
                        <label>51</label>
                        <mixed-citation publication-type="journal">Zhu X, Chu PB, Peyton M, Birnbaumer L. 1995. Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS let 373: 193-198</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
