{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:24:19Z","timestamp":1783607059939,"version":"3.55.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","award":["MUNI\/A\/1684\/2025"],"award-info":[{"award-number":["MUNI\/A\/1684\/2025"]}],"id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Specific University Research"},{"name":"Ministry of Education, Youth and Sports of the Czech Republic","award":["65269705"],"award-info":[{"award-number":["65269705"]}]},{"name":"Ministry of Education, Youth and Sports of the Czech Republic","award":["61388998"],"award-info":[{"award-number":["61388998"]}]},{"DOI":"10.13039\/501100007059","name":"Palack\u00fd University Olomouc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007059","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ELIXIR CZ infrastructure"},{"name":"Ministry of Education, Youth and Sports of the Czech Republic","award":["LM2023055"],"award-info":[{"award-number":["LM2023055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Kv7.1 variants, associated with long QT syndrome type 1 (LQT1) and altering the function of the slow delayed rectifier K+ (IKs) channel, may result in arrhythmias, especially during exercise. This study focused on complex analysis of the R562S-Kv7.1 variant located in helix C of the Kv7.1 C terminus, which was identified in four putatively unrelated families in the Czech Republic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The clinical and genetic investigation was followed by functional analysis (whole-cell patch clamp, confocal microscopy, computational simulations) and structural modelling. The genetic analysis suggested that R562S-Kv7.1 might be a founder LQT1 variant in Central Europe. R562S carriers showed a significantly prolonged corrected QT (QTc) interval at rest and a significantly higher QTc prolongation after exercise vs. healthy relatives. The functional analysis of R562S channels demonstrated their preserved membrane localization, a significant decrease in IKs with a rightward shift of the voltage dependence of activation, and, importantly, a lack of responsiveness to \u03b2-adrenergic stimulation. The latter seems to be related to a modified interaction of the modulatory KCNE1 subunit with Kv7.1. The pro-arrhythmic potential of R562S dysfunction, mediated by delayed afterdepolarizations during \u03b2-adrenergic stimulation, could be effectively prevented by mild (5%) inhibition of L-type Ca2+ current (ICa).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>R562S-Kv7.1 is the first variant in helix C causing an impaired response of IKs channel to \u03b2-adrenergic stimulation, likely due to altered interactions between channel subunits, namely Kv7.1 and KCNE1. Mild ICa inhibition was suggested as a new treatment option.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/europace\/euag156","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:16:29Z","timestamp":1781612189000},"source":"Crossref","is-referenced-by-count":0,"title":["C-terminal long-QT type 1 R562S-Kv7.1 variant, the first variant in helix C impairing \u03b2-adrenergic response of the slow delayed rectifier K+ channel"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3872-2742","authenticated-orcid":false,"given":"Martin","family":"Kr\u00e1l","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Masaryk University , Kamenice 5, Brno 625 00 ,","place":["Czech 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