title: Contribution of BK(Ca)-channel activity in human cardiac fibroblasts to electrical coupling of cardiomyocytes-fibroblasts.
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. Ca(2+)-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 microM: ) or iberiotoxin (200 nM: ). A large-conductance, Ca(2+)-activated K(+) (BK(Ca)) channel with single-channel conductance of 162 +/- 8 pS was also observed in human cardiac fibroblasts. Western blot analysis revealed the presence of alpha-subunit of BK(Ca) 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 BK(Ca) channel is functionally expressed in human cardiac fibroblasts. The activity of these BK(Ca) 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.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University Medical College, No. 1, University Road, Tainan, 701, Taiwan.
authors.forename: Ya-Jean
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ruey J
authors.initials: RJ
authors.lastname: Sung
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wu
mesh_terms: D000200:Action Potentials; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism / Q000502:physiology*; D008962:Models, Theoretical; D032386:Myoblasts, Cardiac / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051419:Paxillin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology
chemical_list: C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051419:Paxillin; D010455:Peptides; D026902:Potassium Channel Blockers; C064719:iberiotoxin