Small-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> current is upregulated via the phosphorylation of CaMKII in cardiac hypertrophy from spontaneously hypertensive rats
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- Kazuya Mizukami
- Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Hisashi Yokoshiki
- Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Hirofumi Mitsuyama
- Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Masaya Watanabe
- Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Taro Tenma
- Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Shingo Takada
- Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Hiroyuki Tsutsui
- Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
書誌事項
- 公開日
- 2015-09-15
- 資源種別
- journal article
- DOI
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- 10.1152/ajpheart.00825.2014
- 公開者
- American Physiological Society
この論文をさがす
説明
<jats:p> Left ventricular hypertrophy is associated with an increased risk of ventricular arrhythmias. However, the underlying molecular basis is poorly understood. It has been reported that small-conductance Ca<jats:sup>2+</jats:sup>-activated K<jats:sup>+</jats:sup> (SK) channels are involved in the pathogenesis of ventricular arrhythmias in heart failure. The present study aimed to test the hypothesis that SK channel activity is increased via the Ca<jats:sup>2+</jats:sup>/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway in hypertensive cardiac hypertrophy. Normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) were used. Whole cell membrane currents were recorded in isolated ventricular myocytes by the patch-clamp method, and apamin-sensitive K<jats:sup>+</jats:sup> current ( I<jats:sub>KAS</jats:sub>), which is inhibited by apamin (100 nM), an SK channel blocker, was evaluated. I<jats:sub>KAS</jats:sub> at 40 mV was present in SHRs, whereas it was hardly detectable in WKY rats (0.579 ± 0.046 vs. 0.022 ± 0.062 pA/pF, both n = 6, P < 0.05). I<jats:sub>KAS</jats:sub> was almost completely abolished by 1 μM KN-93, a CaMKII inhibitor, in SHRs. Optical recordings of left ventricular anterior wall action potentials revealed that apamin prolonged the late phase of repolarization only in SHRs. Western blot analysis of SK channel protein isoforms demonstrated that SK2 was significantly increased in SHRs compared with WKY rats (SK2/GAPDH: 0.66 ± 0.07 vs. 0.40 ± 0.02, both n = 6, P < 0.05), whereas SK1 and SK3 did not differ between groups. In addition, autophosphorylated CaMKII was significantly increased in SHRs (phosphorylated CaMKII/GAPDH: 0.80 ± 0.06 vs. 0.58 ± 0.06, both n = 6, P < 0.05) despite a comparable total amount of CaMKII between groups. In conclusion, SK channels are upregulated via the enhanced activation of CaMKII in cardiac hypertrophy in SHRs. </jats:p>
収録刊行物
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- American Journal of Physiology-Heart and Circulatory Physiology
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American Journal of Physiology-Heart and Circulatory Physiology 309 (6), H1066-H1074, 2015-09-15
American Physiological Society
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キーワード
- Male
- Benzylamines
- Sulfonamides
- Patch-Clamp Techniques
- Small-Conductance Calcium-Activated Potassium Channels
- Action Potentials
- Rats, Inbred WKY
- Rats
- Up-Regulation
- Apamin
- Rats, Inbred SHR
- Animals
- Hypertrophy, Left Ventricular
- Myocytes, Cardiac
- Phosphorylation
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Protein Kinase Inhibitors
詳細情報 詳細情報について
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- CRID
- 1360004236323099776
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- ISSN
- 15221539
- 03636135
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- PubMed
- 26297230
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE