{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:52:47Z","timestamp":1791921167250,"version":"4.3.4"},"reference-count":68,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL142808"],"award-info":[{"award-number":["HL142808"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL146914"],"award-info":[{"award-number":["HL146914"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL138496"],"award-info":[{"award-number":["HL138496"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"\n Key points<\/jats:title>\n \n \n \n \n Endothelial cell TRPV4 (TRPV4\n EC<\/jats:sub>\n ) channels exert a dilatory effect on the resting diameter of resistance mesenteric and pulmonary arteries.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Functional intermediate\u2010 and small\u2010conductance K\n +<\/jats:sup>\n (IK and SK) channels and endothelial nitric oxide synthase (eNOS) are present in the endothelium of mesenteric and pulmonary arteries.\n <\/jats:p>\n <\/jats:list-item>\n \n \n TRPV4\n EC<\/jats:sub>\n sparklets preferentially couple with IK\/SK channels in mesenteric arteries and with eNOS in pulmonary arteries.\n <\/jats:p>\n <\/jats:list-item>\n \n \n TRPV4\n EC<\/jats:sub>\n channels co\u2010localize with IK\/SK channels in mesenteric arteries but not in pulmonary arteries, which may explain TRPV4\n EC<\/jats:sub>\n \u2010IK\/SK channel coupling in mesenteric arteries and its absence in pulmonary arteries.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The presence of the nitric oxide\u2010scavenging protein, haemoglobin \u03b1, limits TRPV4\n EC<\/jats:sub>\n \u2010eNOS signalling in mesenteric arteries.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Spatial proximity of TRPV4\n EC<\/jats:sub>\n channels with eNOS and the absence of haemoglobin \u03b1 favour TRPV4\n EC<\/jats:sub>\n \u2010eNOS signalling in pulmonary arteries.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Abstract<\/jats:title>\n \n Spatially localized Ca\n 2+<\/jats:sup>\n signals activate Ca\n 2+<\/jats:sup>\n \u2010sensitive intermediate\u2010 and small\u2010conductance K\n +<\/jats:sup>\n (IK and SK) channels in some vascular beds and endothelial nitric oxide synthase (eNOS) in others. The present study aimed to uncover the signalling organization that determines selective Ca\n 2+<\/jats:sup>\n signal to vasodilatory target coupling in the endothelium. Resistance\u2010sized mesenteric arteries (MAs) and pulmonary arteries (PAs) were used as prototypes for arteries with predominantly IK\/SK channel\u2010 and eNOS\u2010dependent vasodilatation, respectively. Ca\n 2+<\/jats:sup>\n influx signals through endothelial transient receptor potential vanilloid 4 (TRPV4\n EC<\/jats:sub>\n ) channels played an important role in controlling the baseline diameter of both MAs and PAs. TRPV4\n EC<\/jats:sub>\n channel activity was similar in MAs and PAs. However, the TRPV4 channel agonist GSK1016790A (10\u00a0n\n m<\/jats:sc>\n ) selectively activated IK\/SK channels in MAs and eNOS in PAs, revealing preferential TRPV4\n EC<\/jats:sub>\n \u2010IK\/SK channel coupling in MAs and TRPV4\n EC<\/jats:sub>\n \u2010eNOS coupling in PAs. IK\/SK channels co\u2010localized with TRPV4\n EC<\/jats:sub>\n channels at myoendothelial projections (MEPs) in MAs, although they lacked the spatial proximity necessary for their activation by TRPV4\n EC<\/jats:sub>\n channels in PAs. Additionally, the presence of the NO scavenging protein haemoglobin \u03b1 (Hb\u03b1) within nanometer proximity to eNOS limits TRPV4\n EC<\/jats:sub>\n \u2010eNOS signalling in MAs. By contrast, co\u2010localization of TRPV4\n EC<\/jats:sub>\n channels and eNOS at MEPs, and the absence of Hb\u03b1, favour TRPV4\n EC<\/jats:sub>\n \u2010eNOS coupling in PAs. Thus, our results reveal that differential spatial organization of signalling elements determines TRPV4\n EC<\/jats:sub>\n \u2010IK\/SK\n vs<\/jats:italic>\n . TRPV4\n EC<\/jats:sub>\n \u2010eNOS coupling in resistance arteries.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp279570","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T05:25:05Z","timestamp":1590643505000},"page":"3577-3596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Mechanisms underlying selective coupling of endothelial Ca\n 2+<\/sup>\n signals with eNOS\n vs<\/i>\n . IK\/SK channels in systemic and pulmonary arteries"],"prefix":"10.1113","volume":"598","author":[{"given":"Matteo","family":"Ottolini","sequence":"first","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center University of Virginia\u2010School of Medicine Charlottesville VA USA"},{"name":"Department of Pharmacology University of Virginia\u2010School of Medicine Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdravka","family":"Daneva","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center University of Virginia\u2010School of Medicine Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center University of Virginia\u2010School of Medicine Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Cope","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center University of Virginia\u2010School of Medicine Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh B.","family":"Kasetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience and the North Texas Eye Research Institute University of North Texas Health Science Center Fort Worth TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulab S.","family":"Zode","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience and the North Texas Eye Research Institute University of North Texas Health Science Center Fort Worth TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9587-9342","authenticated-orcid":false,"given":"Swapnil K.","family":"Sonkusare","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center University of Virginia\u2010School of Medicine Charlottesville VA USA"},{"name":"Department of Pharmacology University of Virginia\u2010School of Medicine Charlottesville VA USA"},{"name":"Department of Molecular Physiology and Biological Physics University of Virginia\u2010School of Medicine Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0418OC"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aar3924"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211946109"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1902.sp000911"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407224102"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.10.003"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.165894"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704551"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(90)80902-U"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb13114.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705057"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E17-01-0049"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.2.210"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.2.387"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000074549"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.189530"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12255"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3862"},{"key":"e_1_2_5_20_1","first-page":"H670","article-title":"Comparison of small artery sensitivity and morphology in pressurized and wire\u2010mounted preparations","volume":"268","author":"Falloon BJ","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.9.5746"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00052.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.602532"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106302200"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2015.06.002"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540205000604"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270818"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14762"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.7.634"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310038"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.24.9265"},{"key":"e_1_2_5_32_1","first-page":"e50997","article-title":"Assessing myogenic response and vasoactivity in resistance mesenteric arteries using pressure myography","author":"Jadeja RN","year":"2015","journal-title":"J Vis Exp"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18522"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.002540"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08171"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304-0686PP"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.199br.x"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728220903540257"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0800-04.2004"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9639"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200709875"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801963105"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00040.2005"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1086\/680166"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.08.021"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01500"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007157"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22103"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312933110"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp021086"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00773.2011"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043385"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00140.2015"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0359-11.2011"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171084"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.731679"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02253846"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00463.2006"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07110"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313926"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1216283"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005052"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-174508"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303974"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11626"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005659"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000081980.63146.69"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00418.2011"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12315"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP279570","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP279570","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP279570","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP279570","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:20:26Z","timestamp":1693804826000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP279570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,11]]},"references-count":68,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1113\/JP279570"],"URL":"https:\/\/doi.org\/10.1113\/jp279570","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,11]]},"assertion":[{"value":"2020-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}