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Am J Physiol Gastrointest Liver Physiol ; 304(2): G157-66, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23154976

RESUMO

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.


Assuntos
Ácido Gástrico/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Canal de Potássio KCNQ1/metabolismo , Células Parietais Gástricas/enzimologia , Animais , Membrana Celular/enzimologia , Cromanos/farmacologia , Citoplasma/enzimologia , Endossomos/enzimologia , Transferência Ressonante de Energia de Fluorescência , Histamina/metabolismo , Canal de Potássio KCNQ1/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência , Células Parietais Gástricas/efeitos dos fármacos , Células Parietais Gástricas/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Transporte Proteico , Sulfonamidas/farmacologia , Fatores de Tempo , Proteínas rab de Ligação ao GTP/metabolismo
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