Dataset Information

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

ABSTRACT:

Aims

Fibroblasts, 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 results

Left 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 (3)H-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. Ca(2+)-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.

Conclusions

Fibroblast 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.

SUBMITTER: Wu CT

PROVIDER: S-EPMC4030513 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Wu Chia-Tung CT Qi Xiao-Yan XY Huang Hai H Naud Patrice P Dawson Kristin K Yeh Yung-Hsin YH Harada Masahide M Kuo Chi-Tai CT Nattel Stanley S

Cardiovascular research 20140304 3

<h4>Aims</h4>Fibroblasts, 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).<h4>Methods and results</h4>Left atrial (LA) and ventricular (LV) fibroblasts were freshly isolated from control ...[more]

PMID: 24596399

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Dataset Information

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

Aims

Methods and results

Conclusions

Publications

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

Similar Datasets

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