Disease and region-related cardiac fibroblast potassium current variations and potential functional significance

Chia Tung Wu, Xiao Yan Qi, Hai Huang, Patrice Naud, Kristin Dawson, Yung Hsin Yeh, Masahide Harada, Chi Tai Kuo, Stanley Nattel

研究成果: Article

10 引用 (Scopus)

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AimsFibroblasts, which play an important role in cardiac function/dysfunction, including arrhythmogenesis, have voltage-dependent (Kv) currents of unknown importance. Here, we assessed the differential expression of Kv currents between atrial and ventricular fibroblasts from control dogs and dogs with an atrial arrhythmogenic substrate caused by congestive heart failure (CHF).Methods and resultsLeft atrial (LA) and ventricular (LV) fibroblasts were freshly isolated from control and CHF dogs (2-week ventricular tachypacing, 240 bpm). Kv currents were measured with whole-cell voltage-clamp, mRNA by quantitative polymerase chain reaction (qPCR) and fibroblast proliferation by 3H-thymidine incorporation. Robust voltage-dependent tetraethylammonium (TEA)-sensitive K currents (IC50 ∼1 mM) were recorded. The morphologies and TEA responses of LA and LV fibroblast Kv currents were similar. LV fibroblast Kv-current densities were significantly greater than LA, and Kv-current densities were significantly less in CHF than control. The mRNA expression of Kv-channel subunits Kv1.5 and Kv4.3 was less in LA vs. LV fibroblasts and was down-regulated in CHF, consistent with K-current recordings. Ca2-dependent K-channel subunit (KCa1.1) mRNA and currents were less expressed in LV vs. LA fibroblasts. Inhibiting LA fibroblast K current with 1 mmol/L of TEA or KCa1.1 current with paxilline increased proliferation.ConclusionsFibroblast Kv-current expression is smaller in CHF vs. control, as well as LA vs. LV. KCa1.1 current is greater in LA vs. LV. Suppressing Kv current with TEA enhances fibroblast proliferation, suggesting that Kv current might act to check fibroblast proliferation and that reduced Kv current in CHF may contribute to fibrosis. Fibroblast Kv-current remodelling may play a role in the atrial fibrillation (AF) substrate; modulating fibroblast K channels may present a novel strategy to prevent fibrosis and AF.

元の言語English
ページ(範囲)487-496
ページ数10
ジャーナルCardiovascular Research
102
発行部数3
DOI
出版物ステータスPublished - 01-06-2014
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

これを引用

Wu, C. T., Qi, X. Y., Huang, H., Naud, P., Dawson, K., Yeh, Y. H., Harada, M., Kuo, C. T., & Nattel, S. (2014). Disease and region-related cardiac fibroblast potassium current variations and potential functional significance. Cardiovascular Research, 102(3), 487-496. https://doi.org/10.1093/cvr/cvu055