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Acta Physiologica 2007; Volume 189, Supplement 653
The 86th Annual Meeting of The German Physiological Society
3/25/2007-3/28/2007
Hannover, Germany
A HETEROZYGOUS ENAC MUTATION (AW493R) IDENTIFIED IN PATIENTS WITH ATYPICAL CF INCREASES AMILORIDE-SENSITIVE CURRENTS IN XENOPUS LAEVIS OOCYTES
Abstract number: P08-L6-06
Rauh1 R, Korbmacher1 J, Cuppens2 H, Cassiman2 JJ, Korbmacher1 C
1In. f. Zellulre & Molekulare Physiologie, Universitt Erlangen- Nrnberg,
2Center of Human Genetics, KU Leuven
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. However, in a small number of patients a mutation can be identified only in one CFTR allele. Thus, other factors may contribute to the disease. Interestingly, a heterozygous mutation (W493R) in the a-subunit of the epithelial sodium channel (ENaC) may contribute to the disease phentoype in some patients with atypical CF. We used the Xenopus laevis oocyte expression system to functionally characterise this mutation. In oocytes expressing the mutant channel (aW493R- hENaC) the amiloride sensitive ENaC whole-cell current ([Delta]I ami ) was 3.8 ± 0.3 fold larger than in oocytes expressing wild type ENaC. A corresponding mutation in rat ENaC (aW520R-rENaC) similarly increased [Delta]I ami without increasing channel surface expression measured by a chemiluminescence assay. We conclude that the aW493R mutation results in an increased open probability of ENaC and may contribute to the CF pathophysiology by an inadequate stimulation of Na+ and fluid absorption in the respiratory tract.
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Acta Physiologica 2007; Volume 189, Supplement 653 :P08-L6-06