The pure anti-oestrogen ICI 182,780 (Faslodex™) activates large conductance Ca ²⁺-activated K ⁺ channels in smooth muscle

Oestrogen and tamoxifen activate large conductance Ca ²⁺-activated K ⁺ (BK _Ca) channels in smooth muscle through a non-genomic mechanism that depends on the regulatory β1 subunit and an extracellular binding site. It is unknown whether a 'pure' anti-oestrogen such as ICI 182,780 (Faslodex™), that has no known oestrogenic properties, would have any effect on BK _Ca channels. Using single channel patch clamp techniques on canine colonic myocytes, the hypothesis that ICI 182,780 would activate BK _Ca channels was tested. ICI 182,780 increased the open probability of BK _Ca channels in inside-out patches with an EC ₅₀ of 1 μM. These data suggest that molecules with the ability to bind nuclear oestrogen receptors, regardless of oestrogenic or anti-oestrogenic nature, activate BK _Ca channels through this nongenomic, membrane-delimited mechanism. The identity and characteristics of this putative binding site remain unclear; however, it has pharmacological similarity to oestrogen receptors α and β, as ICI 182,780 interacts with it.