Tetrandrine inhibits Ca2+-activated chloride channel in cultured human umbilical vein endothelial cells.
OBJECTIVE
To characterize the electrophysiological and kinetic properties of Ca2+-activated chloride channel (CaCC) in cultured human umbilical vein endothelial cell line (HUVEC), and test the inhibitory effects of tetrandrine (Tet) on CaCC.


METHODS
Ca2+-activated Cl- currents (I(Cl,Ca)) were recorded by patch-clamp whole cell configurations. [Ca2+]i was measured via intracellular Fura-2 fluorescence intensities.


RESULTS
I(Cl,Ca) was activated by increasing [Ca2+]i via direct elevation of intracellular calcium. I(Cl,Ca) showed an apparent outward rectification properties, and it was activated in a voltage- and calcium-dependent mode. Tet dose-dependently inhibited I(Cl,Ca), the IC50 was (5.2+/-0.4) micromol/L (n=8 cells). Tet suppressed both voltage-dependent and calcium-dependent activation of I(Cl,Ca). The activation time constant was (326+/-12) ms [in the presence of 10 micromol/L Tet, compared to control (175+/-17) ms, at +100 mV], and Ca2+ concentration for half maximal activation was (387+/-61) nmol/L for Tet (compared to control (287+/-36) nmol/L.


CONCLUSIONS
Tet effectively blocked I(Cl,Ca), and such effects might be due to its inhibitory effects on the activation process of Ca2+-activated chloride channel.
Physiological Lab of Hypoxia, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Qi-zhi
QZ
Fang
Ning
N
Zhong
Yi
Y
Zhang
Zhao-nian
ZN
Zhou
D000470:Alkaloids / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018408:Patch-Clamp Techniques; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D000470:Alkaloids; D044182:Benzylisoquinolines; D018118:Chloride Channels; C009438:tetrandrine; D002118:Calcium