{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T03:40:36Z","timestamp":1780717236556,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,20]],"date-time":"2013-12-20T00:00:00Z","timestamp":1387497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Calcium is an important second messenger in eccrine sweating; however, whether modulation of extracellular Ca<jats:sup>2+<\/jats:sup> and Ca<jats:sup>2+<\/jats:sup> entry has the capacity to modulate sweat rate in non\u2010glabrous human skin has not been explored.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Acetylcholine to sweat rate dose\u2013response relationships identify that local <jats:italic>in vivo<\/jats:italic> Ca<jats:sup>2+<\/jats:sup> chelation and L\u2010type Ca<jats:sup>2+<\/jats:sup> channel antagonism have the capacity to attenuate the cholinergic sensitivity of eccrine sweat glands. Importantly, these data translate previous glabrous <jats:italic>in vitro<\/jats:italic> animal studies into non\u2010glabrous <jats:italic>in vivo<\/jats:italic> human skin.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Calcium is an important second messenger in eccrine sweating, with both internal and external sources being identified <jats:italic>in vitro<\/jats:italic>. It is unclear whether <jats:italic>in vivo<\/jats:italic> modulation of extracellular Ca<jats:sup>2+<\/jats:sup> levels or influx has the capacity to modulate sweat rate in non\u2010glabrous human skin. To test the hypothesis that lowering interstitial Ca<jats:sup>2+<\/jats:sup> levels would decrease the sensitivity of the ACh to sweat rate (via capacitance hygrometry) dose\u2013response relationship, nine healthy subjects received six ACh doses (1\u00a0\u00d7\u00a010<jats:sup>\u22125<\/jats:sup> to 1\u00a0\u00d7\u00a010<jats:sup>0<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc> in 10\u2010fold increments) with and without a Ca<jats:sup>2+<\/jats:sup> chelator (12.5\u00a0mg\u00a0ml<jats:sup>\u22121<\/jats:sup> EDTA) via forearm intradermal microdialysis (protocol\u00a01). To test the hypothesis that attenuating Ca<jats:sup>2+<\/jats:sup> influx via L\u2010type Ca<jats:sup>2+<\/jats:sup> channels would also decrease the sensitivity of the ACh to sweat rate dose\u2013response relationship, 10 healthy subjects received similar ACh doses with and without a phenylalkylamine Ca<jats:sup>2+<\/jats:sup> channel blocker (1\u00a0m<jats:sc>m<\/jats:sc> verapamil; protocol\u00a02). Non\u2010linear regression curve fitting identified a right\u2010shifted ED<jats:sub>50<\/jats:sub> in EDTA\u2010treated sites compared with ACh alone (\u22121.0\u00a0\u00b1\u00a00.1 and \u22121.5\u00a0\u00b1\u00a00.1\u00a0log<jats:sc>m<\/jats:sc>, respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), but unchanged maximal sweat rate (0.60\u00a0\u00b1\u00a00.07 and 0.58\u00a0\u00b1\u00a00.11\u00a0mg\u00a0cm<jats:sup>\u22122<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>, respectively; <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05) in protocol\u00a01. Protocol\u00a02 also resulted in a right\u2010shifted ED<jats:sub>50<\/jats:sub> (verapamil, \u22120.9\u00a0\u00b1\u00a00.1\u00a0log<jats:sc>m<\/jats:sc>; ACh alone, \u22121.6\u00a0\u00b1\u00a00.2\u00a0log<jats:sc>m<\/jats:sc>; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), with unchanged maximal sweat rate (verapamil, 0.45\u00a0\u00b1\u00a00.08\u00a0mg\u00a0cm<jats:sup>\u22122<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>; ACh alone, 0.35\u00a0\u00b1\u00a00.06\u00a0mg\u00a0cm<jats:sup>\u22122<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>; <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05). Thus, local <jats:italic>in vivo<\/jats:italic> Ca<jats:sup>2+<\/jats:sup> chelation and L\u2010type Ca<jats:sup>2+<\/jats:sup> channel antagonism have the capacity to attenuate <jats:italic>in vivo<\/jats:italic> cholinergic sensitivity of eccrine sweat glands. These data suggest that interstitial Ca<jats:sup>2+<\/jats:sup> and its influx via Ca<jats:sup>2+<\/jats:sup> channels play a functional role in eccrine sweating in intact non\u2010glabrous human skin.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2013.076547","type":"journal-article","created":{"date-parts":[[2013,11,9]],"date-time":"2013-11-09T04:13:24Z","timestamp":1383970404000},"page":"393-402","source":"Crossref","is-referenced-by-count":34,"title":["Extracellular calcium chelation and attenuation of calcium entry decrease <i>in vivo<\/i> cholinergic\u2010induced eccrine sweating sensitivity in humans"],"prefix":"10.1113","volume":"99","author":[{"given":"Kristen","family":"Metzler\u2010Wilson","sequence":"first","affiliation":[{"name":"Ohio Musculoskeletal and Neurological Institute Ohio University  Athens OH USA"},{"name":"School of Rehabilitation and Communication Sciences Ohio University  Athens OH USA"},{"name":"Marian University College of Osteopathic Medicine  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn L.","family":"Sammons","sequence":"additional","affiliation":[{"name":"Departments of Specialty Medicine Ohio University Heritage College of Osteopathic Medicine  Athens OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Ossim","sequence":"additional","affiliation":[{"name":"School of Rehabilitation and Communication Sciences Ohio University  Athens OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie R.","family":"Metzger","sequence":"additional","affiliation":[{"name":"School of Rehabilitation and Communication Sciences Ohio University  Athens OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Jurovcik","sequence":"additional","affiliation":[{"name":"Ohio Musculoskeletal and Neurological Institute Ohio University  Athens OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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