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Title
  • en Small-conductance Ca2+-activated K+ channel activation deteriorates hypoxic ventricular arrhythmias via CaMKII in cardiac hypertrophy
Alternative
  • en SK channels deteriorate hypoxic ventricular arrhythmia
Creator
    • en Tenma, Taro
    • en Mitsuyama, Hirofumi
    • en Watanabe, Masaya
    • en Kakutani, Naoya
    • en Otsuka, Yutaro
    • en Mizukami, Kazuya
    • en Kamada, Rui
    • en Takahashi, Masayuki
Accessrights open access
Subject
  • Other en Ca2+/calmodulin-dependent protein kinase II (CaMKII)
  • Other en cardiac hypertrophy
  • Other en myocardial hypoxia
  • Other en small-conductance Ca2+-activated K+ (SK) channels
  • Other en ventricular arrhythmia
  • NDC 490
Description
  • Abstract en The molecular and electrophysiological mechanisms of acute ischemic ventricular arrhythmias in hypertrophied hearts are not well known. We hypothesized that small-conductance Ca2+-activated K+ (SK) channels are activated during hypoxia via the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway. We used normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) as a model of cardiac hypertrophy. The inhibitory effects of SK channels and ATP-sensitive K+ channels on electrophysiological changes and genesis of arrhythmias during simulated global hypoxia (GH) were evaluated. Hypoxia-induced abbreviation of action potential duration (APD) occurred earlier in ventricles from SHRs versus. WKY rats. Apamin, a SK channel blocker, prevented this abbreviation in SIIRs in both the early and delayed phase of GH, whereas in WKY rats only the delayed phase was prevented. In contrast, SHRs were less sensitive to glibenclamide, a ATP-sensitive K+ channel blocker, which inhibited the APD abbreviation in both phases of GH in WKY rats. SK channel blockers (apamin and UCL-1684) reduced the incidence of hypoxia-induced sustained ventricular arrhythmias in SHRs but not in WKY rats. Among three SK channel isoforms. SK2 channels were directly coimmunoprecipitated with CaMKII phosphorylated at Thr(286) (p-CaMKII). We conclude that activation of SK channels leads to the APD abbreviation and sustained ventricular arrhythmias during simulated hypoxia, especially in hypertrophied hearts. This mechanism may result from p-CaMKII-bound SK2 channels and reveal new molecular targets to prevent lethal ventricular arrhythmias during acute hypoxia in cardiac hypertrophy. NEW & NOTEWORTHY We now show a new pathophysiological role of small-conductance Ca2+-activated K+ channels, which shorten the action potential duration and induce ventricular arrhythmias during hypoxia. We also demonstrate that small-conductance Ca2+-activated K+ channels interact with phosphorylated Ca2+/calmodulin-dependent protein kinase II at Thr(286) in hypertrophied hearts.
Publisher en American Physiological Society
Date
    Issued2018-08
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/75062
Relation
  • isVersionOf DOI https://doi.org/10.1152/ajpheart.00636.2017
Journal
    • PISSN 0363-6135
      • en American journal of physiology. Heart and circulatory physiology
      • Volume Number315 Issue Number2 Page StartH262 Page EndH272
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Oaidate 2023-07-26