{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:29:05Z","timestamp":1785464945741,"version":"3.56.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,5,18]]},"abstract":"\n Background<\/jats:title>\n \n The tandem of P domains in a weak inward rectifying K+ channel (TWIK)\u2010related acid\u2010sensitive K\n +<\/jats:sup>\n channel (TASK\u20101;\n hK<\/jats:styled-content>\n 2P<\/jats:sub>\n 3.1) two\u2010pore\u2013domain potassium channel was recently shown to regulate the atrial action potential duration. In the human heart,\n TASK<\/jats:styled-content>\n \u20101 channels are specifically expressed in the atria. Furthermore, upregulation of atrial\n TASK<\/jats:styled-content>\n \u20101 currents was described in patients suffering from atrial fibrillation (\n AF<\/jats:styled-content>\n ). We therefore hypothesized that\n TASK<\/jats:styled-content>\n \u20101 channels represent an ideal target for antiarrhythmic therapy of\n AF<\/jats:styled-content>\n . In the present study, we tested the antiarrhythmic effects of the high\u2010affinity\n TASK<\/jats:styled-content>\n \u20101 inhibitor A293 on cardioversion in a porcine model of paroxysmal\n AF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Heterologously expressed human and porcine\n TASK<\/jats:styled-content>\n \u20101 channels are blocked by A293 to a similar extent. Patch clamp measurements from isolated human and porcine atrial cardiomyocytes showed comparable\n TASK<\/jats:styled-content>\n \u20101 currents. Computational modeling was used to investigate the conditions under which A293 would be antiarrhythmic. German landrace pigs underwent electrophysiological studies under general anesthesia. Paroxysmal\n AF<\/jats:styled-content>\n was induced by right atrial burst stimulation. After induction of\n AF<\/jats:styled-content>\n episodes, intravenous administration of A293 restored sinus rhythm within cardioversion times of 177\u00b163 seconds. Intravenous administration of A293 resulted in significant prolongation of the atrial effective refractory period, measured at cycle lengths of 300, 400 and 500\u00a0ms, whereas the surface\n ECG<\/jats:styled-content>\n parameters and the ventricular effective refractory period lengths remained unchanged.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Pharmacological inhibition of atrial\n TASK<\/jats:styled-content>\n \u20101 currents exerts antiarrhythmic effects in vivo as well as in silico\n ,<\/jats:italic>\n resulting in acute cardioversion of paroxysmal\n AF<\/jats:styled-content>\n . Taken together, these experiments indicate the therapeutic potential of A293 for\n AF<\/jats:styled-content>\n treatment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.015751","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T09:30:16Z","timestamp":1589016616000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Pharmacologic TWIK\u2010Related Acid\u2010Sensitive K+ Channel (TASK\u20101) Potassium Channel Inhibitor A293 Facilitates Acute Cardioversion of Paroxysmal Atrial Fibrillation in a Porcine Large Animal Model"],"prefix":"10.1161","volume":"9","author":[{"given":"Felix","family":"Wiedmann","sequence":"first","affiliation":[{"name":"Department of Cardiology University of Heidelberg Germany"},{"name":"DZHK (German Center for Cardiovascular Research) partner site Heidelberg \/Mannheim University of Heidelberg Germany"},{"name":"HCR Heidelberg Center for Heart Rhythm 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