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Barium ions selectively activate BK channels via the Ca 2+ -bowl site

2012; National Academy of Sciences; Volume: 109; Issue: 28 Linguagem: Inglês

10.1073/pnas.1204444109

1091-6490

Yu Zhou, Xuhui Zeng, Christopher J. Lingle,

Neuroscience and Neural Engineering

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.