Modulation of the BK channel by estrogens: examination at single channel level.
BK channels regulate vascular tone by hyperpolarizing smooth muscle in response to fluctuating calcium concentrations. Oestrogen has been reported to lower blood pressure by increasing BK channel open probability through direct binding to the regulatory beta1-subunit(s) associated with the channel. The present investigation demonstrates that 17beta-oestradiol activates the BK channel complex by increasing the burst duration of channel openings. A subconductance state was observed in 25% of recordings following the addition of 17beta-oestradiol and could reflect uncoupling between the pore forming alpha1-subunit and the regulatory beta1-subunit. We also present evidence that more than one beta1-subunit is required to facilitate binding of 17beta-oestradiol to the channel complex.
De Wet
Heidi
H
School of Pharmacy and Biomolecular Sciences, University of Brighton, Oxford, UK.
Allen
Marcus
M
Holmes
Chris
C
Stobbart
Michelle
M
Lippiat
Jonathan D
JD
Callaghan
Richard
R
D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology / Q000379:methods*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D008051:Lipid Bilayers
D004967:Estrogens; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008051:Lipid Bilayers; D004958:Estradiol; D002118:Calcium