{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:26:34Z","timestamp":1791264394268,"version":"4.1.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,2,16]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The \u201csick sinus\u201d syndrome (SSS) is characterized by abnormal formation and\/or propagation of the cardiac impulse. SSS is responsible for about half of the total implantations of electronic pacemakers, which constitute the only currently available therapy for this disorder. We show that genetic ablation or pharmacological inhibition of the muscarinic-gated K\n                    <jats:sup>+<\/jats:sup>\n                    channel (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>KACh<\/jats:italic>\n                    <\/jats:sub>\n                    ) prevents SSS and abolishes atrioventricular block in model mice without affecting the relative degree of heart rate regulation. We propose that \u201ccompensatory\u201d genetic or pharmacological targeting of\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>KACh<\/jats:italic>\n                    <\/jats:sub>\n                    channels may constitute a new paradigm for restoring defects in the balance between inward and outward currents in pacemaker cells. Our study may thus open a new therapeutic perspective to manage dysfunction of formation and conduction of the cardiac impulse.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1517181113","type":"journal-article","created":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T23:45:31Z","timestamp":1454370331000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["G protein-gated\n                    <i>I<\/i>\n                    <sub>\n                      <i>KACh<\/i>\n                    <\/sub>\n                    channels as therapeutic targets for treatment of sick sinus syndrome and heart block"],"prefix":"10.1073","volume":"113","author":[{"given":"Pietro","family":"Mesirca","sequence":"first","affiliation":[{"name":"De\u0301partement de Physiologie, Institut de Genomique Fonctionnelle, Laboratory of Excellence in Ion Channel Science and Therapeutics, UMR-5203, CNRS, F-34094 Montpellier, 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