Tetrandrine inhibits Ca2+-activated chloride channel in cultured human umbilical vein endothelial cells

• Published in: Acta pharmacologica Sinica Vol. 25; no. 3; pp. 327 - 333
• Main Authors: Fang, Qi-zhi, Zhong, Ning, Zhang, Yi, Zhou, Zhao-nian
• Format: Journal Article
• Language: English
• Published: United States 01.03.2004
• Subjects: Alkaloids - pharmacology; Benzylisoquinolines - pharmacology; Calcium - metabolism; Calcium - pharmacology; Cells, Cultured; Chloride Channels - drug effects; Endothelial Cells - cytology; Endothelial Cells - drug effects; Humans; Patch-Clamp Techniques; Umbilical Veins - cytology; Umbilical Veins - drug effects
• ISSN: 1671-4083

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. 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. 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. 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.