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.


RESULTS
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 Ca(2+)-activated K(+) current (BK(Ca)) in most (88%) human cardiac fibroblasts, a delayed rectifier K(+) current (IK(DR)) 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), IC(50) = 7.8 nM), the other was a rapidly inactivated current, relatively resistant to TTX (I(Na.TTXR), IC(50) = 1.8 microM). RT-PCR revealed the molecular identities (mRNAs) of these ion channels in human cardiac fibroblasts, including KCa.1.1 (responsible for BK(Ca)), Kv1.5, Kv1.6 (responsible for IK(DR)), Kv4.2, Kv4.3 (responsible for I(to)), Kir2.1, Kir2.3 (for I(Kir)), Clnc3 (for I(Cl)), Na(V)1.2, Na(V)1.3, Na(V)1.6, Na(V)1.7 (for I(Na.TTX)), and Na(V)1.5 (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.
Li
Gui-Rong
GR
Department of Medicine and Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. grli@hkucc.hku.hk
Sun
Hai-Ying
HY
Chen
Jing-Bo
JB
Zhou
Yuan
Y
Tse
Hung-Fat
HF
Lau
Chu-Pak
CP
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured / Q000378:metabolism; D004594:Electrophysiology / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D007473:Ion Channels / Q000378:metabolism*; D007477:Ions / Q000737:chemistry; D032342:Muscle Cells / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009991:Oscillometry / Q000379:methods; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000737:chemistry
D007473:Ion Channels; D007477:Ions; D012964:Sodium; D002118:Calcium