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Arrhythmogenic β-adrenergic signaling in cardiac hypertrophy : The role of small-conductance calcium-activated potassium channels via activation of CaMKII
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| Title: | Arrhythmogenic β-adrenergic signaling in cardiac hypertrophy : The role of small-conductance calcium-activated potassium channels via activation of CaMKII |
| Authors: | Kamada, Rui Browse this author →KAKEN DB | | Yokoshiki, Hisashi Browse this author →KAKEN DB | | Mitsuyama, Hirofumi Browse this author | | Watanabe, Masaya Browse this author →KAKEN DB | | Mizukami, Kazuya Browse this author | | Tenma, Taro Browse this author →KAKEN DB | | Takahashi, Masayuki Browse this author | | Takada, Shingo Browse this author →KAKEN DB | | Anzai, Toshihisa Browse this author →KAKEN DB |
| Keywords: | SK channels | | β- adrenoreceptor stimulation | | CaMKII | | Cardiac hypertrophy | | Rat |
| Issue Date: | 5-Feb-2019 |
| Publisher: | Elsevier |
| Journal Title: | European journal of pharmacology |
| Volume: | 844 |
| Start Page: | 110 |
| End Page: | 117 |
| Publisher DOI: | 10.1016/j.ejphar.2018.12.011 |
| Abstract: | Sustained ventricular arrhythmias (SVAs) lead to sudden cardiac death, for which β- adrenoreceptor blockers are effective. We hypothesized that electrophysiological changes and arrhythmias by β- adrenoreceptor stimulation are crucially related to activation of small-conductance calcium-activated potassium (SK) channels via the increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity. We used normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs). The latter served as a model of left ventricular hypertrophy. We performed dual optical mapping of action potentials and Ca2+ transients, and the effects of isoproterenol and apamin, an SK channel blocker, were evaluated in the Langendorff-perfused hearts. Action potential duration was abbreviated by isoproterenol (100 nM) in both WKY rats and SHRs. In contrast, the CaMKII activity was increased by isoproterenol only in SHRs. In the presence of isoproterenol, apamin prolonged the action potential duration only in SHRs (n = 10, from 116.6 ± 5.05 ms to 125.4 ± 3.80 ms, P = 0.011), which was prevented by KN-93, a CaMKII inhibitor. Increase in Ca2+ transients and shortening of Ca2+ transient duration by isoproterenol were similarly observed in both animals, which was not affected by apamin. Apamin reduced the isoproterenol-induced SVAs and maximal slope of action potential duration restitution curve specifically in SHRs. In conclusion, β- adrenoreceptor stimulation creates arrhythmogenic substrates via the CaMKII-dependent activation of SK channels in cardiac hypertrophy. |
| Rights: | © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/76694 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 鎌田 塁
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