{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:19:26Z","timestamp":1785295166201,"version":"3.55.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract:<\/jats:title>\n          <jats:p>In human hearts, muscarinic receptors (M-R) are expressed in ventricular and atrial tissue, but the acetylcholine-activated potassium current (I<jats:sub>K,ACh<\/jats:sub>) is expressed mainly in the atrium. M-R activation decreases force and increases electrical stability in human atrium, but the impact of I<jats:sub>K,ACh<\/jats:sub> to both effects remains unclear. We used a new selective blocker of I<jats:sub>K,ACh<\/jats:sub> to elaborate the contribution of I<jats:sub>K,ACh<\/jats:sub> to M-R activation-mediated effects in human atrium. Force and action potentials were measured in rat atria and in human right atrial trabeculae. Cumulative concentration\u2013effect curves for norepinephrine-induced force and arrhythmias were measured in the presence of carbachol (CCh; 1 \u00b5M) or CCh together with the I<jats:sub>K,ACh<\/jats:sub> \u2013blocker XAF-1407 (1 \u00b5M) or in time-matched controls. To investigate the vulnerability to arrhythmias, we performed some experiments also in the presence of cilostamide (0.3 \u00b5M) and rolipram (1 \u00b5M), inhibiting PDE3 and PDE4. In rat atria and human right atrial trabeculae, CCh shortened the action potential duration persistently. However, the direct negative inotropy of CCh was only transient in human, but stable in rat atria. In rat and human atria, the negative inotropic effect was insensitive to blockage of I<jats:sub>K,ACh<\/jats:sub> by XAF-1407. In the presence of cilostamide and rolipram about 40% of trabeculae developed arrhythmias when exposed to norepinephrine. CCh prevented these concentration-dependent norepinephrine-induced arrhythmias, again insensitive to XAF-1407. Maximum catecholamine-induced force was not depressed by CCh. In human atrium, the direct and the indirect negative inotropic effect of CCh are independent of I<jats:sub>K,ACh<\/jats:sub>. The same applies to the CCh-mediated suppression of norepinephrine\/PDE-inhibition-induced arrhythmias.<\/jats:p>","DOI":"10.1097\/fjc.0000000000001237","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T08:51:59Z","timestamp":1645001519000},"page":"678-686","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":11,"title":["Muscarinic Receptor Activation Reduces Force and Arrhythmias in Human Atria Independent of IK,ACh"],"prefix":"10.1097","volume":"79","author":[{"given":"Johannes","family":"Petersen","sequence":"first","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesa","family":"Castro","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"},{"name":"Department of Cardiology, University Heart Center L\u00fcbeck, Medical Clinic II, University Hospital Schleswig-Holstein;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne K. P.","family":"Bengaard","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Pecha","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djemail","family":"Ismaili","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"},{"name":"Department of Cardiology, University Heart and Vascular Center, Hamburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-3385","authenticated-orcid":false,"given":"Carl","family":"Schulz","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jascha","family":"Sahni","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Steenpass","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Meier","sequence":"additional","affiliation":[{"name":"Division of Cardiology\/Angiology\/Intensive Care, EVK D\u00fcsseldorf. Institute of Neural and Sensory Physiology, cNEP, Cardiac Neuro- and Electrophysiology Research Consortium, Heinrich Heine University D\u00fcsseldorf, Medical Faculty, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Reichenspurner","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Heart and Vascular Center, Hamburg, Germany;"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jespersen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Eschenhagen","sequence":"additional","affiliation":[{"name":"Institute of Experimental 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