Structural basis for calcium and magnesium regulation of a large conductance calcium-activated potassium channel with ?1 subunits.

ABSTRACT: Large conductance Ca(2+)- and voltage-activated potassium (BK) channels, composed of pore-forming ? subunits and auxiliary ? subunits, play important roles in diverse physiological activities. The ?1 is predominately expressed in smooth muscle cells, where it greatly enhances the Ca(2+) sensitivity of BK channels for proper regulation of smooth muscle tone. However, the structural basis underlying dynamic interaction between BK mSlo1 ? and ?1 remains elusive. Using macroscopic ionic current recordings in various Ca(2+) and Mg(2+) concentrations, we identified two binding sites on the cytosolic N terminus of ?1, namely the electrostatic enhancing site (mSlo1(K392,R393)-?1(E13,T14)), increasing the calcium sensitivity of BK channels, and the hydrophobic site (mSlo1(L906,L908)-?1(L5,V6,M7)), passing the physical force from the Ca(2+) bowl onto the enhancing site and S6 C-linker. Dynamic binding of these sites affects the interaction between the cytosolic domain and voltage-sensing domain, leading to the reduction of Mg(2+) sensitivity. A comprehensive structural model of the BK(mSlo1 ?-?1) complex was reconstructed based on these functional studies, which provides structural and mechanistic insights for understanding BK gating.

SUBMITTER: Liu HW 

PROVIDER: S-EPMC4059135 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature