title: TASK-2 K₂p K⁺ channel: thoughts about gating and its fitness to physiological function.
abstract: TASK-2 (K2P5) was one of the earliest members of the K2P two-pore, four transmembrane domain K(+) channels to be identified. TASK-2 gating is controlled by changes in both extra- and intracellular pH through separate sensors: arginine 224 and lysine 245, located at the extra- and intracellular ends of transmembrane domain 4. TASK-2 is inhibited by a direct effect of CO2 and is regulated by and interacts with G protein subunits. TASK-2 takes part in regulatory adjustments and is a mediator in the chemoreception process in neurons of the retrotrapezoid nucleus where its pHi sensitivity could be important in regulating excitability and therefore signalling of the O2/CO2 status. Extracellular pH increases brought about by HCO3 (-) efflux from proximal tubule epithelial cells have been proposed to couple to TASK-2 activation to maintain electrochemical gradients favourable to HCO3 (-) reabsorption. We demonstrate that, as suspected previously, TASK-2 is expressed at the basolateral membrane of the same proximal tubule cells that express apical membrane Na(+)-H(+)-exchanger NHE-3 and basolateral membrane Na(+)-HCO3 (-) cotransporter NBCe1-A, the main components of the HCO3 (-) transport machinery. We also discuss critically the mechanism by which TASK-2 is modulated and impacts the process of HCO3 (-) reclaim by the proximal tubule epithelium, concluding that more than a mere shift in extracellular pH is probably involved.
authors.affiliation: Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, 5110466, Valdivia, Chile.
authors.forename: Karen I
authors.initials: KI
authors.lastname: López-Cayuqueo
authors.forename: Gaspar
authors.initials: G
authors.lastname: Peña-Münzenmayer
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Niemeyer
authors.forename: Francisco V
authors.initials: FV
authors.lastname: Sepúlveda
authors.forename: L Pablo
authors.initials: LP
authors.lastname: Cid
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D024683:Potassium Channels, Tandem Pore Domain