Barium ions selectively activate BK channels via the Ca²⁺-bowl site
2012
Zhou, Yu | Zeng, Xu-Hui | Lingle, Christopher J.
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.
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