{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:12:53Z","timestamp":1784041973212,"version":"3.55.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,11,3]],"date-time":"2014-11-03T00:00:00Z","timestamp":1414972800000},"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":"crossref","award":["R01HL107084"],"award-info":[{"award-number":["R01HL107084"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National institutes of Health","doi-asserted-by":"crossref","award":["P01HL090554"],"award-info":[{"award-number":["P01HL090554"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Key points<\/jats:title><jats:sec><jats:label\/><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) augments distinct inspiratory motor patterns, generated within the preB\u00f6tzinger complex (preB\u00f6tC), in a dose\u2010dependent way. The frequency of sighs and gasping are stimulated at low concentrations, while the frequency of eupnoea increases only at high concentrations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We used <jats:italic>in vivo<\/jats:italic> microinjections into the preB\u00f6tC and <jats:italic>in vitro<\/jats:italic> isolated brainstem slice preparations to investigate the dose\u2010dependent effects of PGE<jats:sub>2<\/jats:sub> on the preB\u00f6tC activity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Synaptic measurements in whole cell voltage clamp recordings of inspiratory neurons revealed no changes in inhibitory or excitatory synaptic transmission in response to PGE<jats:sub>2<\/jats:sub> exposure.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In current clamp recordings obtained from inspiratory neurons of the preB\u00f6tC, we found an increase in the frequency and amplitude of bursting activity in neurons with intrinsic bursting properties after exposure to PGE<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Riluzole, a blocker of the persistent sodium current, abolished the effect of PGE<jats:sub>2<\/jats:sub> on sigh activity, while flufenamic acid, a blocker of the calcium\u2010activated non\u2010selective cation conductance, abolished the effect on eupnoeic activity caused by PGE<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Prostaglandins are important regulators of autonomic functions in the mammalian organism. Here we demonstrate <jats:italic>in vivo<\/jats:italic> that prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) can differentially increase the frequency of eupnoea (normal breathing) and sighs (augmented breaths) when injected into the preB\u00f6tzinger complex (preB\u00f6tC), a medullary area that is critical for breathing. Low concentrations of PGE<jats:sub>2<\/jats:sub> (100\u2013300\u00a0n<jats:sc>m<\/jats:sc>) increased the sigh frequency, while higher concentrations (1\u20132\u00a0\u03bc<jats:sc>m<\/jats:sc>) were required to increase the eupnoeic frequency. The concentration\u2010dependent effects were similarly observed in the isolated preB\u00f6tC. This <jats:italic>in vitro<\/jats:italic> preparation also revealed that riluzole, a blocker of the persistent sodium current (<jats:italic>I<\/jats:italic><jats:sub>Nap<\/jats:sub>), abolished the modulatory effect on sighs, while flufenamic acid, an antagonist for the calcium\u2010activated non\u2010selective cation conductance (<jats:italic>I<\/jats:italic><jats:sub>CAN<\/jats:sub>) abolished the effect of PGE<jats:sub>2<\/jats:sub> on fictive eupnoea at higher concentrations. At the cellular level PGE<jats:sub>2<\/jats:sub> significantly increased the amplitude and frequency of intrinsic bursting in inspiratory neurons. By contrast PGE<jats:sub>2<\/jats:sub> affected neither excitatory nor inhibitory synaptic transmission. We conclude that PGE<jats:sub>2<\/jats:sub> differentially modulates sigh, gasping and eupnoeic activity by differentially increasing <jats:italic>I<\/jats:italic><jats:sub>Nap<\/jats:sub> and <jats:italic>I<\/jats:italic><jats:sub>CAN<\/jats:sub> currents in preB\u00f6tC neurons.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.279794","type":"journal-article","created":{"date-parts":[[2014,10,4]],"date-time":"2014-10-04T02:03:05Z","timestamp":1412388185000},"page":"305-319","source":"Crossref","is-referenced-by-count":38,"title":["Prostaglandin E<sub>2<\/sub> differentially modulates the central control of eupnoea, sighs and gasping in mice"],"prefix":"10.1113","volume":"593","author":[{"given":"Henner","family":"Koch","sequence":"first","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle WA 98101 USA"},{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98104 USA"},{"name":"Department of Neurology University of T\u00fcbingen, Hertie Institute for Clinical Brain Research  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cali","family":"Caughie","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle WA 98101 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank P.","family":"Elsen","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle WA 98101 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Doi","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle WA 98101 USA"},{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"3rd","given":"Alfredo J.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle WA 98101 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Zanella","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle WA 98101 USA"},{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Marino","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research, Seattle Children's Research Institute  Seattle WA 98101 USA"},{"name":"Department of Neurological Surgery University of Washington  Seattle WA 98104 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