Barium ions selectively activate BK channels via the Ca2+-bowl site.
Activation of Ca(2+)-dependent BK channels is increased via binding of micromolar Ca(2+) to two distinct high-affinity sites per BK α-subunit. One site, termed the Ca(2+) bowl, is embedded within the second RCK domain (RCK2; regulator of conductance for potassium) of each α-subunit, while oxygen-containing residues in the first RCK domain (RCK1) have been linked to a separate Ca(2+) ligation site. Although both sites are activated by Ca(2+) and Sr(2+), Cd(2+) selectively favors activation via the RCK1 site. Divalent cations of larger ionic radius than Sr(2+) are thought to be ineffective at activating BK channels. Here we show that Ba(2+), better known as a blocker of K(+) channels, activates BK channels and that this effect arises exclusively from binding at the Ca(2+)-bowl site. Compared with previous estimates for Ca(2+) bowl-mediated activation by Ca(2+), the affinity of Ba(2+) to the Ca(2+) bowl is reduced about fivefold, and coupling of binding to activation is reduced from ∼3.6 for Ca(2+) to about ∼2.8 for Ba(2+). These results support the idea that ionic radius is an important determinant of selectivity differences among different divalent cations observed for each Ca(2+)-binding site.
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Yu
Y
Zhou
Xu-Hui
XH
Zeng
Christopher J
CJ
Lingle
D000495:Allosteric Site; D000818:Animals; D001464:Barium / Q000737:chemistry*; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002412:Cations; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D007477:Ions; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D015221:Potassium Channels / Q000737:chemistry; D013324:Strontium / Q000737:chemistry; D014982:Xenopus laevis
D002412:Cations; D007477:Ions; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D001464:Barium; D002118:Calcium; D013324:Strontium