{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:33:48Z","timestamp":1791225228146,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>\n                      This study was designed to establish the pathology\u2010specific inhibitory effects of the\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Kur<\/jats:sub>\n                      \/\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>to<\/jats:sub>\n                      \/\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>K,ACh<\/jats:sub>\n                      blocker AVE0118 on atrium\u2010selective channels and its corresponding effects on action potential shape and effective refractory period in patients with chronic AF (cAF).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>\n                      Outward K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010currents of right atrial myocytes and action potentials of atrial trabeculae were measured with whole\u2010cell voltage clamp and microelectrode techniques, respectively. Outward currents were dissected by curve fitting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>\n                      Four components of outward K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010currents and AF\u2010specific alterations in their properties were identified.\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>to<\/jats:sub>\n                      was smaller in cAF than in SR, and AVE0118 (10\u2003\u03bc\n                      <jats:sc>M<\/jats:sc>\n                      ) apparently accelerated its inactivation in both groups without reducing its amplitude. Amplitudes of rapidly and slowly inactivating components of\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Kur<\/jats:sub>\n                      were lower in cAF than in SR. The former was abolished by AVE0118 in both groups, the latter was partially blocked in SR, but not in cAF, even though its inactivation was apparently accelerated in cAF. The large non\u2010inactivating current component was similar in magnitude in both groups, but decreased by AVE0118 only in SR. AVE0118 strongly suppressed AF\u2010related constitutively active\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>K,ACh<\/jats:sub>\n                      and prolonged atrial action potential and effective refractory period exclusively in cAF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications<\/jats:title>\n                    <jats:p>\n                      In atrial myocytes of cAF patients, we detected reduced function of distinct\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>Kur<\/jats:sub>\n                      components that possessed decreased component\u2010specific sensitivity to AVE0118 most likely as a consequence of AF\u2010induced electrical remodelling. Inhibition of profibrillatory constitutively active\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>K,ACh<\/jats:sub>\n                      may lead to pathology\u2010specific efficacy of AVE0118 that is likely to contribute to its ability to convert AF into SR.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                      (2008)\n                      <jats:bold>154<\/jats:bold>\n                      , 1619\u20131630; doi:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.209\">10.1038\/bjp.2008.209<\/jats:ext-link>\n                      ; published online 9 June 2008\n                    <\/jats:p>\n                  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