Smooth muscle relaxation and activation of the large conductance <scp><scp>Ca</scp>⁺⁺</scp> – activated <scp><scp>K</scp>⁺</scp> (<scp>BK_Ca</scp>) channel by novel oestrogens

Abstract

The novel oestrogens were able to relax smooth muscle, but through different mechanisms. In particular, oestrone oxime required the presence of the endothelium to exert much of its effect, whilst Quat DME-oestradiol depended both on NO and BK(Ca) channel activation. The activation of BK(Ca) currents in HEK 293 cells expressing hSloα+β1 by Quat DME-oestradiol is consistent with an extracellular binding site between the two subunits. The binding site resides between the extracellular N terminal of the α subunit and the extracellular loop between TM1 and 2 of the β1 subunit. Membrane-impermeant Quat DME-oestradiol lacks an exchangeable hydrogen on the A ring obviating antioxidant activity.