Document Detail


Separate gating mechanisms mediate the regulation of K2P potassium channel TASK-2 by intra- and extracellular pH.
MedLine Citation:
PMID:  20351106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
TASK-2 (KCNK5 or K(2P)5.1) is a background K(+) channel that is opened by extracellular alkalinization and plays a role in renal bicarbonate reabsorption and central chemoreception. Here, we demonstrate that in addition to its regulation by extracellular protons (pH(o)) TASK-2 is gated open by intracellular alkalinization. The following pieces of evidence suggest that the gating process controlled by intracellular pH (pH(i)) is independent from that under the command of pH(o). It was not possible to overcome closure by extracellular acidification by means of intracellular alkalinization. The mutant TASK-2-R224A that lacks sensitivity to pH(o) had normal pH(i)-dependent gating. Increasing extracellular K(+) concentration acid shifts pH(o) activity curve of TASK-2 yet did not affect pH(i) gating of TASK-2. pH(o) modulation of TASK-2 is voltage-dependent, whereas pH(i) gating was not altered by membrane potential. These results suggest that pH(o), which controls a selectivity filter external gate, and pH(i) act at different gating processes to open and close TASK-2 channels. We speculate that pH(i) regulates an inner gate. We demonstrate that neutralization of a lysine residue (Lys(245)) located at the C-terminal end of transmembrane domain 4 by mutation to alanine abolishes gating by pH(i). We postulate that this lysine acts as an intracellular pH sensor as its mutation to histidine acid-shifts the pH(i)-dependence curve of TASK-2 as expected from its lower pK(a). We conclude that intracellular pH, together with pH(o), is a critical determinant of TASK-2 activity and therefore of its physiological function.
Authors:
María Isabel Niemeyer; L Pablo Cid; Gaspar Peña-Münzenmayer; Francisco V Sepúlveda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-29
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-24     Completed Date:  2010-06-17     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16467-75     Citation Subset:  IM    
Affiliation:
Centro de Estudios Científicos, Valdivia 5110566, Chile. miniemeyer@cecs.cl
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Electrophysiology / methods
Gene Expression Regulation*
Humans
Hydrogen-Ion Concentration
Kidney Tubules / metabolism*
Lysine / chemistry
Mice
Models, Biological
Molecular Sequence Data
Potassium / chemistry
Potassium Channels, Tandem Pore Domain / metabolism*
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Sulfates / chemistry
Chemical
Reg. No./Substance:
0/Kcnk5 protein, mouse; 0/Potassium Channels, Tandem Pore Domain; 0/Sulfates; 56-87-1/Lysine; 7440-09-7/Potassium
Comments/Corrections

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