{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:15:14Z","timestamp":1753892114914,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the primary reason for heart transplantation; upward of 70% of DCM cases are considered idiopathic. Our <jats:italic>in-vitro<\/jats:italic> experiments showed that reduced hybrid\/complex N-glycosylation in mouse cardiomyocytes is linked with DCM. Further, we observed direct effects of reduced N-glycosylation on K<jats:sub>v<\/jats:sub> gating. However, it is difficult to rigorously determine the effects of glycosylation on K<jats:sub>v<\/jats:sub> activity, because there are multiple K<jats:sub>v<\/jats:sub> isoforms in cardiomyocytes contributing to the cardiac excitation. Due to complex functions of K<jats:sub>v<\/jats:sub> isoforms, only the sum of K<jats:sup>+<\/jats:sup> currents (I<jats:sub>Ksum<\/jats:sub>) can be recorded experimentally and decomposed later using exponential fitting to estimate component currents, such as I<jats:sub>Kto<\/jats:sub>, I<jats:sub>Kslow<\/jats:sub>, and I<jats:sub>Kss<\/jats:sub>. However, such estimation cannot adequately describe glycosylation effects and K<jats:sub>v<\/jats:sub> mechanisms. Here, we propose a framework of simulation modeling of K<jats:sub>v<\/jats:sub> kinetics in mouse ventricular myocytes and model calibration using the <jats:italic>in-vitro<\/jats:italic> data under normal and reduced glycosylation conditions through ablation of the Mgat1 gene (i.e., Mgat1KO). Calibrated models facilitate the prediction of K<jats:sub>v<\/jats:sub> characteristics at different voltages that are not directly observed in the <jats:italic>in-vitro<\/jats:italic> experiments. A model calibration procedure is developed based on the genetic algorithm. Experimental results show that, in the Mgat1KO group, both I<jats:sub>Kto<\/jats:sub> and I<jats:sub>Kslow<\/jats:sub> densities are shown to be significantly reduced and the rate of I<jats:sub>Kslow<\/jats:sub> inactivation is much slower. The proposed approach has strong potential to couple simulation models with experimental data for gaining a better understanding of glycosylation effects on K<jats:sub>v<\/jats:sub> kinetics.<\/jats:p>","DOI":"10.3389\/fphys.2022.816651","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T10:04:40Z","timestamp":1646388280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Simulation Modeling of Reduced Glycosylation Effects on Potassium Channels of Mouse Cardiomyocytes"],"prefix":"10.3389","volume":"13","author":[{"given":"Haedong","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Ednie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric S.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1016\/S0002-9440(10)61153-4","article-title":"Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cdna microarray","volume":"160","author":"Barrans","year":"2002","journal-title":"Am. 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