Progesterone activation of β₁-containing BK channels involves two binding sites.

ABSTRACT: Progesterone (≥1 µM) is used in recovery of cerebral ischemia, an effect likely contributed to by cerebrovascular dilation. The targets of this progesterone action are unknown. We report that micromolar (µM) progesterone activates mouse cerebrovascular myocyte BK channels; this action is lost in β₁^-/- mice myocytes and in lipid bilayers containing BK α subunit homomeric channels but sustained on β₁/β₄-containing heteromers. Progesterone binds to both regulatory subunits, involving two steroid binding sites conserved in β₁-β₄: high-affinity (sub-µM), which involves Trp87 in β₁ loop, and low-affinity (µM) defined by TM1 Tyr32 and TM2 Trp163. Thus progesterone, but not its oxime, bridges TM1-TM2. Mutation of the high

SUBMITTER: North KC 

PROVIDER: S-EPMC10636063 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature