CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes.
J Physiol
; 564(Pt 3): 671-82, 2005 May 01.
Article
en En
| MEDLINE
| ID: mdl-15746174
The cystic fibrosis transmembrane conductance regulator (CFTR) plays a crucial role in regulating fluid secretion by the airways, intestines, sweat glands and other epithelial tissues. It is well established that the CFTR is a cAMP-activated, nucleotide-dependent anion channel, but additional functions are often attributed to it, including regulation of the epithelial sodium channel (ENaC). The absence of CFTR-dependent ENaC inhibition and the resulting sodium hyperabsorption were postulated to be a major electrolyte transport abnormality in cystic fibrosis (CF)-affected epithelia. Several ex vivo studies, including those that used the Xenopus oocyte expression system, have reported ENaC inhibition by activated CFTR, but contradictory results have also been obtained. Because CFTR-ENaC interactions have important implications in the pathogenesis of CF, the present investigation was undertaken by our three independent laboratories to resolve whether CFTR regulates ENaC in oocytes and to clarify potential sources of previously reported dissimilar observations. Using different experimental protocols and a wide range of channel expression levels, we found no evidence that activated CFTR regulates ENaC when oocyte membrane potential was carefully clamped. We determined that an apparent CFTR-dependent ENaC inhibition could be observed when resistance in series with the oocyte membrane was not low enough or the feedback voltage gain was not high enough. We suggest that the inhibitory effect of CFTR on ENaC reported in some earlier oocyte studies could be attributed to problems arising from high levels of channel expression and suboptimal recording conditions, that is, large series resistance and/or insufficient feedback voltage gain.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oocitos
/
Canales de Sodio
/
Activación del Canal Iónico
/
AMP Cíclico
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Técnicas de Placa-Clamp
/
Regulador de Conductancia de Transmembrana de Fibrosis Quística
Tipo de estudio:
Clinical_trials
/
Evaluation_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Physiol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido