Characterization of Multiple Ion Channels in Cultured Human Cardiac Fibroblasts

Background: Although fibroblast-to-myocyte electrical coupling is experimentally suggested, electrophysiology of cardiac fibroblasts is not as well established as contractile cardiac myocytes. The present study was therefore designed to characterize ion channels in cultured human cardiac fibroblasts. Methods and Findings: A whole-cell patch voltage clamp technique and RT-PCR were employed to determine ion channels expression and their molecular identities. We found that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts. These include a big conductance Ca2+-activated K+ current (BKCa) in most (88%) human cardiac fibroblasts, a delayed rectifier K+ current (IKDR) and a transient outward K+ current (I-to) in a small population (15 and 14%, respectively) of cells, an inwardly-rectifying K+ current (I-Kir) in 24% of cells, and a chloride current (I-Cl) in 7% of cells under isotonic conditions. In addition, two types of voltage-gated Na+ currents (I-Na) with distinct properties were present in most (61%) human cardiac fibroblasts. One was a slowly inactivated current with a persistent component, sensitive to tetrodotoxin (TTX) inhibition (I-Na.TTX, IC50 = 7.8 nM), the other was a rapidly inactivated current, relatively resistant to TTX (I-Na.TTXR, IC50 = 1.8 mu M). RT-PCR revealed the molecular identities (mRNAs) of these ion channels in human cardiac fibroblasts, including KCa.1.1 (responsible for BKCa), Kv1.5, Kv1.6 (responsible for IKDR), Kv4.2, Kv4.3 (responsible for I-to), Kir2.1, Kir2.3 (for I-Kir), Clnc3 (for I-Cl), NaV1.2, NaV1.3, NaV1.6, NaV1.7 (for I-Na.TTX), and NaV1.5 (for I-Na.TTXR). Conclusions: These results provide the first information that multiple ion channels are present in cultured human cardiac fibroblasts, and suggest the potential contribution of these ion channels to fibroblast-myocytes electrical coupling.