{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:12:21Z","timestamp":1791209541007,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1999,10,29]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent protein kinases II (CaMKII) have important functions in regulating cardiac excitability and contractility. In the present study, we examined whether CaMKII regulated the transient outward K<jats:sup>+<\/jats:sup>current (<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>) in whole-cell patch-clamped human atrial myocytes. We found that a specific CaMKII inhibitor, KN-93 (20 \u03bcmol\/L), but not its inactive analog, KN-92, accelerated the inactivation of<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>(\u03c4<jats:sub>fast<\/jats:sub>: 66.9\u00b14.4 versus 43.0\u00b14.4 ms, n=35;<jats:italic>P<\/jats:italic>&lt;0.0001) and inhibited its maintained component (at +60 mV, 4.9\u00b10.4 versus 2.8\u00b10.4 pA\/pF, n=35;<jats:italic>P<\/jats:italic>&lt;0.0001), leading to an increase in the extent of its inactivation. Similar effects were observed by dialyzing cells with a peptide corresponding to CaMKII residues 281 to 309 or with autocamtide-2\u2013related inhibitory peptide and by external application of the calmodulin inhibitor calmidazolium, which also suppressed the effects of KN-93. Furthermore, the phosphatase inhibitor okadaic acid (500 nmol\/L) slowed<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>inactivation, increased<jats:italic>I<\/jats:italic><jats:sub>sus<\/jats:sub>, and inhibited the effects of KN-93. Changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>by dialyzing cells with \u224830 nmol\/L Ca<jats:sup>2+<\/jats:sup>or by using the fast Ca<jats:sup>2+<\/jats:sup>buffer BAPTA had opposite effects on<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>. In BAPTA-loaded myocytes,<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>was less sensitive to KN-93. In myocytes from patients in chronic atrial fibrillation, characterized by a prominent<jats:italic>I<\/jats:italic><jats:sub>sus<\/jats:sub>, KN-93 still increased the extent of inactivation of<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>. Western blot analysis of atrial samples showed that \u03b4-CaMKII expression was enhanced during chronic atrial fibrillation. In conclusion, CaMKII control the extent of inactivation of<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>in human atrial myocytes, a process that could contribute to<jats:italic>I<\/jats:italic><jats:sub>to<\/jats:sub>alterations observed during chronic atrial fibrillation.<\/jats:p>","DOI":"10.1161\/01.res.85.9.810","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"810-819","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":133,"title":["Regulation of the Transient Outward K<sup>+<\/sup>Current by Ca<sup>2+<\/sup>\/Calmodulin-Dependent Protein Kinases II in Human Atrial Myocytes"],"prefix":"10.1161","volume":"85","author":[{"given":"Sophie","family":"Tessier","sequence":"first","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Karczewski","sequence":"additional","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst-Georg","family":"Krause","sequence":"additional","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Pansard","sequence":"additional","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Acar","sequence":"additional","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Lang-Lazdunski","sequence":"additional","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Mercadier","sequence":"additional","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ste\u0301phane N.","family":"Hatem","sequence":"additional","affiliation":[{"name":"From INSERM Unite\u0301 460 (S.T., J.-J.M., S.N.H.), Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France; Max-Delbru\u0308ck Centre for Molecular Medicine (P.K., E.-G.K.), Berlin-Buch, Germany; and Service de Chirurgie Cardiaque (Y.P., C.A., M.L.-L.), Ho\u0302pital Xavier Bichat, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.4.548"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.80.6.772"},{"key":"e_1_3_2_3_2","first-page":"H142","volume":"252","year":"1987","unstructured":"Escande D, Coulombe A, Faivre J-F, Deroubaix E, Coraboeuf E. 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