{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T08:03:27Z","timestamp":1764403407741,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Development and Innovation Office","award":["NKFIH-K138090","NKFIH-K142764","NKFIH-K147301","EK\u00d6P-24-4-I-DE-455","EK\u00d6P-24-3-II-DE-154"],"award-info":[{"award-number":["NKFIH-K138090","NKFIH-K142764","NKFIH-K147301","EK\u00d6P-24-4-I-DE-455","EK\u00d6P-24-3-II-DE-154"]}]},{"name":"University of Debrecen Program for Scientific Publication","award":["NKFIH-K138090","NKFIH-K142764","NKFIH-K147301","EK\u00d6P-24-4-I-DE-455","EK\u00d6P-24-3-II-DE-154"],"award-info":[{"award-number":["NKFIH-K138090","NKFIH-K142764","NKFIH-K147301","EK\u00d6P-24-4-I-DE-455","EK\u00d6P-24-3-II-DE-154"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several ion currents in the mammalian ventricular myocardium are substantially regulated by the sympathetic nervous system via \u03b2-adrenergic receptor activation, including the slow delayed rectifier K+ current and the L-type calcium current. This study investigated the downstream mechanisms of \u03b2-adrenergic receptor stimulation by isoproterenol (ISO) on the inward rectifier (IK1) and the rapid delayed rectifier (IKr) K+ currents using action potential voltage clamp (APVC) and conventional voltage clamp techniques in isolated canine left ventricular cardiomyocytes. IK1 and IKr were dissected by 50 \u00b5M BaCl2 and 1 \u00b5M E-4031, respectively. Acute application of 10 nM ISO significantly increased IK1 under the plateau phase of the action potential (0\u2013+20 mV) using APVC, and similar results were obtained with conventional voltage clamp. However, \u03b2-adrenergic receptor stimulation did not affect the peak current density flowing during terminal repolarization or the overall IK1 integral. The ISO-induced enhancement of IK1 was blocked by the calcium\/calmodulin kinase II (CaMKII) inhibitor KN-93 (1 \u00b5M) but not by the protein kinase A inhibitor H-89 (3 \u00b5M). Neither KN-93 nor H-89 affected the IK1 density under baseline conditions (in the absence of ISO). In contrast, parameters of the IKr current were not affected by \u03b2-adrenergic receptor stimulation with ISO. These findings suggest that sympathetic activation enhances IK1 in canine left ventricular cells through the CaMKII pathway, while IKr remains unaffected under the experimental conditions used.<\/jats:p>","DOI":"10.3390\/ijms252111609","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T06:29:57Z","timestamp":1730183397000},"page":"11609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beta-Adrenergic Activation of the Inward Rectifier K+ Current Is Mediated by the CaMKII Pathway in Canine Ventricular Cardiomyocytes"],"prefix":"10.3390","volume":"25","author":[{"given":"Zsigmond M\u00e1t\u00e9","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-8446","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Csaba","family":"Dienes","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f3zsef","family":"\u00d3v\u00e1ri","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8521-5152","authenticated-orcid":false,"given":"D\u00e9nes","family":"Kiss","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"H\u00e9zs\u0151","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-9567","authenticated-orcid":false,"given":"Norbert","family":"Szentandr\u00e1ssy","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Magyar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3894-0738","authenticated-orcid":false,"given":"Tam\u00e1s","family":"B\u00e1ny\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter P\u00e1l","family":"N\u00e1n\u00e1si","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1113\/jphysiol.1995.sp020842","article-title":"Beta-adrenergic and cholinergic modulation of inward rectifier K+ channel function and phosphorylation in guinea-pig ventricle","volume":"486","author":"Koumi","year":"1995","journal-title":"J. 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