{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:31:46Z","timestamp":1791048706094,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,7,9]],"date-time":"2008-07-09T00:00:00Z","timestamp":1215561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Aim:\u2002<\/jats:bold> We compared the clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in domain II (S5\u2010S6) of human, hNa<jats:sub>v<\/jats:sub>1.5, cardiac Na<jats:sup>+<\/jats:sup> channels.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Full clinical evaluation of pedigree members through three generations of a Chinese family combined with <jats:italic>SCN5A<\/jats:italic> sequencing from genomic DNA was compared with patch and voltage\u2010clamp results from two independent expression systems.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> The four mutation carriers showed bradycardia, and slowed sino\u2010atrial, atrioventricular and intraventricular conduction. Two also showed sick sinus syndrome; two had ST elevation in leads V1 and V2. Unlike WT\u2010hNa<jats:sub>v<\/jats:sub>1.5, whole\u2010cell patch\u2010clamped HEK293 cells expressing R878C\u2010hNa<jats:sub>v<\/jats:sub>1.5 showed no detectable Na<jats:sup>+<\/jats:sup> currents (<jats:italic>i<\/jats:italic><jats:sub>Na<\/jats:sub>), even with substitution of a similarly charged lysine residue. Voltage\u2010clamped <jats:italic>Xenopus<\/jats:italic> oocytes injected with either 0.04 or 1.5\u2003\u03bcg\u2003\u03bcL<jats:sup>\u22121<\/jats:sup> R878C\u2010hNa<jats:sub>v<\/jats:sub>1.5 cRNA similarly showed no <jats:italic>i<\/jats:italic><jats:sub>Na<\/jats:sub>, yet WT\u2010hNa<jats:sub>v<\/jats:sub>1.5 cRNA diluted to 0.0004\u20130.0008\u2003ng\u2003\u03bcL<jats:sup>\u22121<\/jats:sup>resulted in expression of detectable <jats:italic>i<\/jats:italic><jats:sub>Na<\/jats:sub>. <jats:italic>i<\/jats:italic><jats:sub>Na<\/jats:sub> was simply determined by the amount of injected WT\u2010hNa<jats:sub>v<\/jats:sub>1.5: doubling the dose of WT\u2010hNa<jats:sub>v<\/jats:sub>1.5 cRNA doubled <jats:italic>i<\/jats:italic><jats:sub>Na<\/jats:sub>. <jats:italic>i<\/jats:italic><jats:sub>Na<\/jats:sub> amplitudes and activation and inactivation characteristics were similar irrespective of whether WT\u2010hNa<jats:sub>v<\/jats:sub>1.5 cRNA was given alone or combined with equal doses of R878C\u2010hNa<jats:sub>v<\/jats:sub>1.5 cRNA therefore excluding dominant negative phenotypic effects. Na<jats:sup>+<\/jats:sup> channel function in HEK293 cells transfected with R878C\u2010hNa<jats:sub>v<\/jats:sub>1.5 was not restored by exposure to mexiletine (200\u2003\u03bc<jats:sc>m<\/jats:sc>) and lidocaine (100\u2003\u03bc<jats:sc>m<\/jats:sc>). Fluorescence confocal microscopy using E3\u2010Nav1.5 antibody demonstrated persistent membrane expression of both WT and R878C\u2010hNa<jats:sub>v<\/jats:sub>1.5. Modelling studies confirmed that such <jats:italic>i<\/jats:italic><jats:sub>Na<\/jats:sub> reductions reproduced the SSS phenotype.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Clinical consequences of the novel R878C mutation correlate with results of physiological studies.<\/jats:p>","DOI":"10.1111\/j.1748-1716.2008.01883.x","type":"journal-article","created":{"date-parts":[[2008,7,8]],"date-time":"2008-07-08T15:45:38Z","timestamp":1215531938000},"page":"311-323","source":"Crossref","is-referenced-by-count":34,"title":["Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na<sup>+<\/sup> channel"],"prefix":"10.1111","volume":"194","author":[{"given":"Y.","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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