Activation of Ca2+-dependent BK channels is increased via binding of micromolar Ca2+ to two distinct high-affinity sites per BK α-subunit. One site, termed the Ca2+ 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 Ca2+ ligation site. Although both sites are activated by Ca2+ and Sr2+, Cd2+ selectively favors activation via the RCK1 site. Divalent cations of larger ionic radius than Sr2+ are thought to be ineffective at activating BK channels. Here we show that Ba2+, better known as a blocker of K+ channels, activates BK channels and that this effect arises exclusively from binding at the Ca2+-bowl site. Compared with previous estimates for Ca2+ bowl-mediated activation by Ca 2+, the affinity of Ba2+ to the Ca2+ bowl is reduced about fivefold, and coupling of binding to activation is reduced from ∼3.6 for Ca2+ to about ∼2.8 for Ba2+. These results support the idea that ionic radius is an important determinant of selectivity differences among different divalent cations observed for each Ca2+-binding site.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Jul 10 2012|
- Allosteric regulation
- Slo1 channels