An extracellular ion pathway plays a central role in the cooperative gating of a K(2P) K+ channel by extracellular pH.
J Biol Chem
; 288(8): 5984-91, 2013 Feb 22.
Article
in En
| MEDLINE
| ID: mdl-23319597
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ion Channel Gating
/
Potassium Channels, Tandem Pore Domain
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biol Chem
Year:
2013
Document type:
Article
Affiliation country: