Stretch-activated cation channel in human umbilical vein endothelium in normal pregnancy and in preeclampsia.
OBJECTIVE
To determine whether stretch-activated cation channels (SAC) are present in intact human umbilical vein endothelium (HUVE) and in an endothelial cell line (EA.hy) and whether they act as endothelial mechanosensors, and to determine whether endothelial SAC in HUVE from women with pregnancies complicated by preeclampsia undergo functional changes compared with those in HUVE from women with normotensive pregnancies.


RESULTS
By use of the patch-clamp technique we identified a SAC in intact HUVE and in an endothelial cell line. The SAC had mean conductances of 29+/-5 pS (n = 38) for K+ and 12+/-2 pS (n = 4) for Ca2+. Administration of 50 micromol/I gadolinium, a blocker of mechanosensitive ion channels, completely blocked activity of this channel. We found from single-channel recordings that influx of Ca2+ through SAC directly activated high-conductance Ca2+-dependent potassium channels, proving that a significant influx of Ca2+ through SAC occurs at physiologic concentrations of Ca2+. In a comparative study, apparent channel density of SAC (percentage of patches with SAC activity) in HUVE from women with pregnancies complicated by preeclampsia (36.2 +/- 4.3%) was twofold higher than that in HUVE from women with normal pregnancies (17.9+/-2.9%, P< 0.01). Channel conductance and sensitivity to stretching of SAC were not altered by preeclampsia.


CONCLUSIONS
Since SAC are capable of acting as endothelial mechanosensors, the greater than normal density of SAC associated with preeclampsia might reflect an alteration of mechanotransduction.
Köhler
R
R
Department of Internal Medicine and Nephrology, University Hospital Benjamin Franklin, Free University, Berlin, Germany.
Schönfelder
G
G
Hopp
H
H
Distler
A
A
Hoyer
J
J
D000328:Adult; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D002412:Cations; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D015398:Signal Transduction; D014471:Umbilical Veins / Q000378:metabolism*
D002412:Cations; D007473:Ion Channels; D005682:Gadolinium; D011188:Potassium; D002118:Calcium