{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:25:00Z","timestamp":1792787100924,"version":"4.5.0"},"reference-count":58,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Biophotonics Imaging Platform"},{"name":"HEA Programme for Research in Third Level Institutions (PRTLI) Cycle 4"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Tonic contractions of rabbit urethra are associated with spontaneous electrical slow waves that are thought to originate in pacemaker cells termed interstitial cells of Cajal (ICC).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            ICC pacemaker activity results from their ability to generate propagating Ca\n                            <jats:sup>2+<\/jats:sup>\n                            waves, although the exact mechanisms of propagation are not understood.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            In this study, we have identified spontaneous localised Ca\n                            <jats:sup>2+<\/jats:sup>\n                            events for the first time in urethral ICC; these were due to Ca\n                            <jats:sup>2+<\/jats:sup>\n                            release from the endoplasmic reticulum (ER) via ryanodine receptors (RyRs) and, while they often remained localised, they sometimes initiated propagating Ca\n                            <jats:sup>2+<\/jats:sup>\n                            waves.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We show that propagation of Ca\n                            <jats:sup>2+<\/jats:sup>\n                            waves in urethral ICC is critically dependent upon Ca\n                            <jats:sup>2+<\/jats:sup>\n                            influx via reverse mode NCX.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our data provide a clearer understanding of the intracellular mechanisms involved in the generation of ICC pacemaker activity.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Interstitial cells of Cajal (ICC) are putative pacemaker cells in the rabbit urethra. Pacemaker activity in ICC results from spontaneous propagating Ca\n                      <jats:sup>2+<\/jats:sup>\n                      waves that are modulated by [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      and whose propagation is inhibited by inositol tri\u2010phosphate receptor (IP\n                      <jats:sub>3<\/jats:sub>\n                      R) blockers. The purpose of this study was to further examine the role of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release in the propagation of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      waves. Intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      was measured in Fluo\u20104\u2010loaded ICC using a Nipkow spinning disc confocal microscope at fast acquisition rates (50\u00a0fps). We identified previously undetected localised Ca\n                      <jats:sup>2+<\/jats:sup>\n                      events originating from ryanodine receptors (RyRs). Inhibiting Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx by removing [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      or blocking reverse mode sodium\u2013calcium exchange (NCX) with KB\u2010R 7943 or SEA\u20100400 abolished Ca\n                      <jats:sup>2+<\/jats:sup>\n                      waves, while localised Ca\n                      <jats:sup>2+<\/jats:sup>\n                      events persisted. Stimulating RyRs with 1\u00a0m\n                      <jats:sc>m<\/jats:sc>\n                      caffeine restored propagation. Propagation was also inhibited when Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release sites were uncoupled by buffering intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      with EGTA\u2010AM. This was reversed when Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx via NCX was increased by reducing [Na\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      to 13\u00a0m\n                      <jats:sc>m<\/jats:sc>\n                      . Low [Na\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      also increased the frequency of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      waves and this effect was blocked by tetracaine and ryanodine but not 2\u2010aminoethoxydiphenyl borate (2\u2010APB). RT\u2010PCR revealed that isolated ICC expressed both RyR\n                      <jats:sub>2<\/jats:sub>\n                      and RyR\n                      <jats:sub>3<\/jats:sub>\n                      subtypes. We conclude: (i) RyRs are required for the initiation of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      waves, but wave propagation normally depends on activation of IP\n                      <jats:sub>3<\/jats:sub>\n                      Rs; (ii) under resting conditions, propagation by IP\n                      <jats:sub>3<\/jats:sub>\n                      Rs requires sensitisation by influx of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      via reverse mode NCX; (iii) propagation can be maintained by RyRs if they have been sensitised to Ca\n                      <jats:sup>2+<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp270883","type":"journal-article","created":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T08:49:25Z","timestamp":1433494165000},"page":"3333-3350","source":"Crossref","is-referenced-by-count":34,"title":["The role of Ca\n                    <sup>2+<\/sup>\n                    influx in spontaneous Ca\n                    <sup>2+<\/sup>\n                    wave propagation in interstitial cells of Cajal from the rabbit urethra"],"prefix":"10.1113","volume":"593","author":[{"given":"Bernard T.","family":"Drumm","sequence":"first","affiliation":[{"name":"Smooth Muscle Research Centre Dundalk Institute of Technology  Dundalk Co. Louth Ireland"},{"name":"Department of Molecular Medicine, Royal College of Surgeons in Ireland Beaumont Hospital  Dublin 9 Ireland"},{"name":"Department of Physiology and Cell Biology University of Nevada School of Medicine  Reno Nevada 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roddy J.","family":"Large","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre Dundalk Institute of Technology  Dundalk Co. Louth Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Hollywood","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre Dundalk Institute of Technology  Dundalk Co. Louth Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Thornbury","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre Dundalk Institute of Technology  Dundalk Co. 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