Independent trafficking of the KCNQ1 K+ channel and H+-K+-ATPase in gastric parietal cells from mice.
Am J Physiol Gastrointest Liver Physiol
; 304(2): G157-66, 2013 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-23154976
ABSTRACT
Gastric acid secretion by the H(+)-K(+)-ATPase at the apical surface of activated parietal cells requires luminal K(+) provided by the KCNQ1/KCNE2 K(+) channel. However, little is known about the trafficking and relative spatial distribution of KCNQ1 and H(+)-K(+)-ATPase in resting and activated parietal cells and the capacity of KCNQ1 to control acid secretion. Here we show that inhibition of KCNQ1 activity quickly curtails gastric acid secretion in vivo, even when the H(+)-K(+)-ATPase is permanently anchored in the apical membrane, demonstrating a key role of the K(+) channel in controlling acid secretion. Three-dimensional imaging analysis of isolated mouse gastric units revealed that the majority of KCNQ1 resides in an intracytoplasmic, Rab11-positive compartment in resting parietal cells, distinct from H(+)-K(+)-ATPase-enriched tubulovesicles. Upon activation, there was a significant redistribution of H(+)-K(+)-ATPase and KCNQ1 from intracytoplasmic compartments to the apical secretory canaliculi. Significantly, high Förster resonance energy transfer was detected between H(+)-K(+)-ATPase and KCNQ1 in activated, but not resting, parietal cells. These findings demonstrate that H(+)-K(+)-ATPase and KCNQ1 reside in independent intracytoplasmic membrane compartments, or membrane domains, and upon activation of parietal cells, both membrane proteins are transported, possibly via Rab11-positive recycling endosomes, to apical membranes, where the two molecules are closely physically opposed. In addition, these studies indicate that acid secretion is regulated by independent trafficking of KCNQ1 and H(+)-K(+)-ATPase.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Células Parietais Gástricas
/
ATPase Trocadora de Hidrogênio-Potássio
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Canal de Potássio KCNQ1
/
Ácido Gástrico
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Gastrointest Liver Physiol
Assunto da revista:
FISIOLOGIA
/
GASTROENTEROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Austrália