Modulation of Ca2+-activated K+ channels in human vascular cells by insulin and basic fibroblast growth factor.
Insulin and basic fibroblast growth factor (bFGF) play an important role in the pathogenesis of atherosclerosis and have been shown to have vasodilatory effects. Since modulation of vascular ion channels determines membrane potential and thereby influences essential Ca2+-dependent intracellular pathways, we have investigated the effect of insulin and bFGF on Ca2+-activated K+ channels (BKCa) in human umbilical vein endothelial cells (HUVEC) and smooth muscle cells. The latter were obtained from either atherosclerotic plaques (SMCP) or from media segments (SMCM) of human coronary arteries. Using the patch-clamp technique, insulin (100 microU/ml) caused a significant increase in BKCa open-state probability in SMCP and HUVEC, whereas no significant changes were observed in SMCM. Basic FGF (30 ng/ml) revealed a significant increase in BKCa activity in HUVEC and a significant decrease in the BKCa open-state probability in SMCP, but caused no changes in SMCM. Thus, growth factors modulate vascular BKCa in a cell-type specific manner, which may be of importance concerning vasoactive and atherogenic effects of growth factors.
Wiecha
J
J
Dept of Cardiology, University of Ulm, Germany.
Reineker
K
K
Reitmayer
M
M
Voisard
R
R
Hannekum
A
A
Mattfeldt
T
T
Waltenberger
J
J
Hombach
V
V
D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003331:Coronary Vessels; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms / Q000494:pharmacology; D014471:Umbilical Veins
D007328:Insulin; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; D016222:Fibroblast Growth Factor 2; C064719:iberiotoxin