The effects of tetrandrine, a blocker of voltage-dependent Ca2+ channels, on ionic currents were investigated in an endothelial cell line (HUV-EC-C) originally derived from human umbilical vein. In whole-cell configuration, tetrandrine (0.5-50 μM) reversibly decreased the amplitude of K+ outward currents. The IC50 value of tetrandrine-induced decrease in outward current was 5μM. The K+ outward current in response to depolarizing voltage pulses was also inhibited by iberiotoxin (200 nM), yet not by glibenclamide (10μM) or apamin (200 nM). The reduced amplitude of outward current by tetrandrine can be reversed by the further addition of Evans' blue (30μM) or niflumic acid (30 μM). Thus, the tetrandrine-sensitive component of outward current is believed to be Ca2+-activated K+ current. Pretreatment with thapsigargin (1 μM) or sodium nitroprusside (10 μM) for 5 h did not prevent tetrandrine-mediated inhibition of outward current. In outside-out configuration, bath application of tetrandrine (5 μM) did not change the single-channel conductance but significantly reduced the opening probability of large-conductance Ca2+-activated K+ (BK(Ca)) channels. The tetrandrine-mediated decrease in the channel activity was independent on internal Ca2+ concentration. Tetrandrine (5 μM) can also shift the activation curve of BK(Ca) channels to more positive potentials by approximately 20 mV. The change in the kinetic behavior of BK(Ca) channels caused by tetrandrine is due to a decrease in mean open time and an increase in mean closed time. The present study provides substantial evidence that tetrandrine is capable of suppressing the activity of BK(Ca) channels in endothelial cells. The direct inhibition of these channels by tetrandrine should contribute to its effect on the functional activities of endothelial cells.
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 2000 Jan 1|
All Science Journal Classification (ASJC) codes
- Molecular Medicine