{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:47:38Z","timestamp":1790218058019,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:00:00Z","timestamp":1384905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>A new class of interstitial cells, PDGFR\u03b1<jats:sup>+<\/jats:sup> cells, is distributed densely in the proximal stomachs of mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>PDGFR\u03b1<jats:sup>+<\/jats:sup> cells express the molecular apparatus necessary for transduction of inputs from enteric inhibitory motor neurons.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>PDGFR\u03b1<jats:sup>+<\/jats:sup> cells generate spontaneous Ca<jats:sup>2+<\/jats:sup> transients and display dynamic Ca<jats:sup>2+<\/jats:sup> oscillations in response to purines.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Purinergic responses are mediated by P2Y1 receptors and by Ca<jats:sup>2+<\/jats:sup> release from intracellular Ca<jats:sup>2+<\/jats:sup> stores.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ca<jats:sup>2+<\/jats:sup> release in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells is the likely means by which purinergic neurotransmitters activate Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels (SK) and hyperpolarization in GI muscles to elicit inhibitory motor responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Spontaneous Ca<jats:sup>2+<\/jats:sup> transients may be a means of regulating basal excitability of fundus muscles and release of purines from motor neurons may contribute to the control of pressure during filling in the proximal stomach.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold> Platelet\u2010derived growth factor receptor \u03b1 positive (PDGFR\u03b1<jats:sup>+<\/jats:sup>) cells are suggested to mediate purinergic inputs in GI muscles, but the responsiveness of these cells to purines <jats:italic>in situ<\/jats:italic> has not been evaluated. We developed techniques to label and visualize PDGFR\u03b1<jats:sup>+<\/jats:sup> cells in murine gastric fundus, load cells with Ca<jats:sup>2+<\/jats:sup> indicators, and follow their activity via digital imaging. Immunolabelling demonstrated a high density of PDGFR\u03b1<jats:sup>+<\/jats:sup> cells in the fundus. Cells were isolated and purified by fluorescence\u2010activated cell sorting (FACS) using endogenous expression of enhanced green fluorescent protein (eGFP) driven off the <jats:italic>Pdgfra<\/jats:italic> promoter. Quantitative PCR showed high levels of expression of purinergic P2Y1 receptors and SK3 K<jats:sup>+<\/jats:sup> channels in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells. Ca<jats:sup>2+<\/jats:sup> imaging was used to characterize spontaneous Ca<jats:sup>2+<\/jats:sup> transients and responses to purines in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells <jats:italic>in situ<\/jats:italic>. ATP, ADP, UTP and \u03b2\u2010NAD elicited robust Ca<jats:sup>2+<\/jats:sup> transients in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells. Ca<jats:sup>2+<\/jats:sup> transients were also elicited by the P2Y1\u2010specific agonist (<jats:italic>N<\/jats:italic>)\u2010methanocarba\u20102MeSADP (MRS\u20102365), and inhibited by MRS\u20102500, a P2Y1\u2010specific antagonist. Responses to ADP, MRS\u20102365 and \u03b2\u2010NAD were absent in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells from <jats:italic>P2ry1<jats:sup>(\u2212\/\u2212)<\/jats:sup><\/jats:italic> mice, but responses to ATP were retained. Purine\u2010evoked Ca<jats:sup>2+<\/jats:sup> transients were mediated through Ca<jats:sup>2+<\/jats:sup> release mechanisms. Inhibitors of phospholipase C (U\u201073122), IP3 (2\u2010APB), ryanodine receptors (Ryanodine) and SERCA pump (cyclopiazonic acid and thapsigargin) abolished Ca<jats:sup>2+<\/jats:sup> transients elicited by purines. This study provides a link between purine binding to P2Y1 receptors and activation of SK3 channels in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells. Activation of Ca<jats:sup>2+<\/jats:sup> release is likely to be the signalling mechanism in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells responsible for the transduction of purinergic enteric inhibitory input in gastric fundus muscles.<\/jats:p>","DOI":"10.1113\/jphysiol.2013.264747","type":"journal-article","created":{"date-parts":[[2013,10,22]],"date-time":"2013-10-22T01:23:42Z","timestamp":1382405022000},"page":"6193-6208","source":"Crossref","is-referenced-by-count":95,"title":["Distribution and Ca<sup>2+<\/sup> signalling of fibroblast\u2010like (PDGFR\u03b1<sup>+<\/sup>) cells in the murine gastric fundus"],"prefix":"10.1113","volume":"591","author":[{"given":"Salah A.","family":"Baker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant W.","family":"Hennig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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