{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:48:07Z","timestamp":1783648087718,"version":"3.55.0"},"reference-count":89,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["HL146969"],"award-info":[{"award-number":["HL146969"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormalities in G-protein-gated inwardly rectifying potassium (GIRK) channels have been implicated in diseased states of the cardiovascular system; however, the role of GIRK4 (Kir3.4) in cardiac physiology and pathophysiology has yet to be completely understood. Within the heart, the KACh channel, consisting of two GIRK1 and two GIRK4 subunits, plays a major role in modulating the parasympathetic nervous system\u2019s influence on cardiac physiology. Being that GIRK4 is necessary for the functional KACh channel, KCNJ5, which encodes GIRK4, it presents as a therapeutic target for cardiovascular pathology. Human variants in KCNJ5 have been identified in familial hyperaldosteronism type III, long QT syndrome, atrial fibrillation, and sinus node dysfunction. Here, we explore the relevance of KCNJ5 in each of these diseases. Further, we address the limitations and complexities of discerning the role of KCNJ5 in cardiovascular pathophysiology, as identical human variants of KCNJ5 have been identified in several diseases with overlapping pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms241310849","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:43:30Z","timestamp":1688085810000},"page":"10849","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Relevance of KCNJ5 in Pathologies of Heart Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Karisa M.","family":"Meyer","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Cardiac Surgery, The Ohio State University, Columbus, OH 43210, USA"},{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2748-6747","authenticated-orcid":false,"given":"Nipun","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Cardiac Surgery, The Ohio State University, Columbus, OH 43210, USA"},{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung seo","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Cardiac Surgery, The Ohio State University, Columbus, OH 43210, USA"},{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3989-0920","authenticated-orcid":false,"given":"Mona","family":"El Refaey","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Cardiac Surgery, The Ohio State University, Columbus, OH 43210, USA"},{"name":"The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/374135a0","article-title":"The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+-channel proteins","volume":"374","author":"Krapivinsky","year":"1995","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"26086","DOI":"10.1074\/jbc.270.44.26086","article-title":"Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels","volume":"270","author":"Ferrer","year":"1995","journal-title":"J. Biol. 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