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Contribution of BKCa-Channel Activity in Human Cardiac Fibroblasts to Electrical Coupling of Cardiomyocytes-Fibroblasts

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Abstract

Cardiac fibroblasts are involved in the maintenance of myocardial tissue structure. However, little is known about ion currents in human cardiac fibroblasts. It has been recently reported that cardiac fibroblasts can interact electrically with cardiomyocytes through gap junctions. Ca2+-activated K+ currents (I K[Ca]) of cultured human cardiac fibroblasts were characterized in this study. In whole-cell configuration, depolarizing pulses evoked I K(Ca) in an outward rectification in these cells, the amplitude of which was suppressed by paxilline (1 μM) or iberiotoxin (200 nM). A large-conductance, Ca2+-activated K+ (BKCa) channel with single-channel conductance of 162 ± 8 pS was also observed in human cardiac fibroblasts. Western blot analysis revealed the presence of α-subunit of BKCa channels. The dynamic Luo-Rudy model was applied to predict cell behavior during direct electrical coupling of cardiomyocytes and cardiac fibroblasts. In the simulation, electrically coupled cardiac fibroblasts also exhibited action potential; however, they were electrically inert with no gap-junctional coupling. The simulation predicts that changes in gap junction coupling conductance can influence the configuration of cardiac action potential and cardiomyocyte excitability. I k(Ca) can be elicited by simulated action potential waveforms of cardiac fibroblasts when they are electrically coupled to cardiomyocytes. This study demonstrates that a BKCa channel is functionally expressed in human cardiac fibroblasts. The activity of these BKCa channels present in human cardiac fibroblasts may contribute to the functional activities of heart cells through transfer of electrical signals between these two cell types.

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Acknowledgement

The authors thank Han-Dong Chang for technical assistance. This work was partly aided by grants from the National Science Council (NSC-93-2320B-006-055 and NSC-94-2320B-006-019), Taiwan.

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, National Cheng Kung University Medical College, No. 1, University Road, Tainan, 701, Taiwan

    Ya-Jean Wang, Ming-Wei Lin & Sheng-Nan Wu

  2. Department of Medicine, National Cheng Kung University Medical College, No. 1, University Road, Tainan, 701, Taiwan

    Ruey J. Sung

  3. Department of Physiology, National Cheng Kung University Medical College, No. 1, University Road, Tainan, 701, Tainan, Taiwan

    Sheng-Nan Wu

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  1. Ya-Jean Wang
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Correspondence to Sheng-Nan Wu.

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Wang, YJ., Sung, R.J., Lin, MW. et al. Contribution of BKCa-Channel Activity in Human Cardiac Fibroblasts to Electrical Coupling of Cardiomyocytes-Fibroblasts. J Membrane Biol 213, 175–185 (2006). https://doi.org/10.1007/s00232-007-0027-8

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  • DOI: https://doi.org/10.1007/s00232-007-0027-8

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