An extracellular ion pathway plays a central role in the cooperative gating of a K(2P) K+ channel by extracellular pH. 


Author: González W, Zúñiga L, Cid LP, Arévalo B, Niemeyer MI, Sepúlveda FV.

Affiliation: Centro de Estudios Científicos (CECs), 5110466 Valdivia, Chile. 
Conference/Journal: J Biol Chem.
Date published: 2013 Feb 22
Other:
 Volume ID: 288   ,  Issue ID: 8   ,  Pages: 5984-91   ,  Special Notes: doi: 10.1074/jbc.M112.445528   ,  Word Count: 148  
    

Proton-gated TASK-3 K(+) channel belongs to the K(2P) family of proteins that underlie the K(+) leak setting the membrane potential in all cells. TASK-3 is under cooperative gating control by extracellular [H(+)]. Use of recently solved K(2P) structures allows us to explore the molecular mechanism of TASK-3 cooperative pH gating. Tunnel-like side portals define an extracellular ion pathway to the selectivity filter. We use a combination of molecular modeling and functional assays to show that pH-sensing histidine residues and K(+) ions mutually interact electrostatically in the confines of the extracellular ion pathway. K(+) ions modulate the pK(a) of sensing histidine side chains whose charge states in turn determine the open/closed transition of the channel pore. Cooperativity, and therefore steep dependence of TASK-3 K(+) channel activity on extracellular pH, is dependent on an effect of the permeant ion on the channel pH(o) sensors.

PMID: 23319597