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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)487-496
Number of pages10
JournalCardiovascular Research
Volume102
Issue number3
DOIs
Publication statusPublished - 01-06-2014

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Potassium
Fibroblasts
Tetraethylammonium
Heart Failure
Dogs
Atrial Fibrillation
Messenger RNA
Fibrosis
Thymidine
Inhibitory Concentration 50
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

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

Cite this

Wu, Chia Tung ; Qi, Xiao Yan ; Huang, Hai ; Naud, Patrice ; Dawson, Kristin ; Yeh, Yung Hsin ; Harada, Masahide ; Kuo, Chi Tai ; Nattel, Stanley. / Disease and region-related cardiac fibroblast potassium current variations and potential functional significance. In: Cardiovascular Research. 2014 ; Vol. 102, No. 3. pp. 487-496.
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title = "Disease and region-related cardiac fibroblast potassium current variations and potential functional significance",
abstract = "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.",
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Disease and region-related cardiac fibroblast potassium current variations and potential functional significance. / Wu, Chia Tung; Qi, Xiao Yan; Huang, Hai; Naud, Patrice; Dawson, Kristin; Yeh, Yung Hsin; Harada, Masahide; Kuo, Chi Tai; Nattel, Stanley.

In: Cardiovascular Research, Vol. 102, No. 3, 01.06.2014, p. 487-496.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Disease and region-related cardiac fibroblast potassium current variations and potential functional significance

AU - Wu, Chia Tung

AU - Qi, Xiao Yan

AU - Huang, Hai

AU - Naud, Patrice

AU - Dawson, Kristin

AU - Yeh, Yung Hsin

AU - Harada, Masahide

AU - Kuo, Chi Tai

AU - Nattel, Stanley

PY - 2014/6/1

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N2 - 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.

AB - 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.

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