{"status":"public","date_updated":"2024-06-30T13:57:07Z","doi":"10.1159/000272059","date_created":"2024-06-30T13:56:57Z","intvolume":"        25","abstract":[{"lang":"eng","text":"Loss-of-function mutations of the epithelial sodium channel (ENaC) may contribute to pulmonary symptoms resembling those of patients with atypical cystic fibrosis (CF). Recently, we identified a loss-of-function mutation in the alpha-subunit of ENaC (alphaF61L) in an atypical CF patient without mutations in CFTR. To investigate the functional effect of this mutation, we expressed human wild-type alpha beta gamma-ENaC or mutant alpha(F61L) beta gamma-ENaC in Xenopus laevis oocytes. The alphaF61L mutation reduced the ENaC mediated whole-cell currents by approximately 90%. In contrast, the mutation decreased channel surface expression only by approximately 40% and did not alter the single-channel conductance. These findings indicate that the major effect of the mutation is a reduction of the average channel open probability (P(o)). This was confirmed by experiments using the betaS520C mutant ENaC which can be converted to a channel with a P(o) of nearly one, and by experiments using chymotrypsin to proteolytically activate the channel. These experiments revealed that the mutation reduced the average P(o) of ENaC by approximately 75%. Na(+) self inhibition of the mutant channel was significantly enhanced, but the observed effect was too small to account for the large reduction in average channel P(o). The ENaC-activator S3969 partially rescued the loss-of-function phenotype of the alphaF61L mutation. We conclude that the alphaF61L mutation may contribute to respiratory symptoms in atypical CF patients."}],"publication":"Cellular Physiology and Biochemistry","page":"145–158","citation":{"ama":"Huber R, Krueger B, Diakov A, et al. Functional Characterization of a Partial Loss-of-Function Mutation of the Epithelial Sodium Channel (ENaC) Associated with Atypical Cystic Fibrosis. <i>Cellular Physiology and Biochemistry</i>. 2010;25(001):145–158. doi:<a href=\"https://doi.org/10.1159/000272059\">10.1159/000272059</a>","bibtex":"@article{Huber_Krueger_Diakov_Korbmacher_Haerteis_Einsiedel_Gmeiner_Azad_Cuppens_Cassiman_et al._2010, title={Functional Characterization of a Partial Loss-of-Function Mutation of the Epithelial Sodium Channel (ENaC) Associated with Atypical Cystic Fibrosis}, volume={25}, DOI={<a href=\"https://doi.org/10.1159/000272059\">10.1159/000272059</a>}, number={001}, journal={Cellular Physiology and Biochemistry}, publisher={S. Karger AG}, author={Huber, Regina and Krueger, Bettina and Diakov, Alexei and Korbmacher, Judit and Haerteis, Silke and Einsiedel, Jürgen and Gmeiner, Peter and Azad, Abul and Cuppens, Harry and Cassiman, Jean-Jaques and et al.}, year={2010}, pages={145–158} }","short":"R. Huber, B. Krueger, A. Diakov, J. Korbmacher, S. Haerteis, J. Einsiedel, P. Gmeiner, A. Azad, H. Cuppens, J.-J. Cassiman, C. Korbmacher, R. Rauh, Cellular Physiology and Biochemistry 25 (2010) 145–158.","mla":"Huber, Regina, et al. “Functional Characterization of a Partial Loss-of-Function Mutation of the Epithelial Sodium Channel (ENaC) Associated with Atypical Cystic Fibrosis.” <i>Cellular Physiology and Biochemistry</i>, vol. 25, no. 001, S. Karger AG, 2010, pp. 145–158, doi:<a href=\"https://doi.org/10.1159/000272059\">10.1159/000272059</a>.","chicago":"Huber, Regina, Bettina Krueger, Alexei Diakov, Judit Korbmacher, Silke Haerteis, Jürgen Einsiedel, Peter Gmeiner, et al. “Functional Characterization of a Partial Loss-of-Function Mutation of the Epithelial Sodium Channel (ENaC) Associated with Atypical Cystic Fibrosis.” <i>Cellular Physiology and Biochemistry</i> 25, no. 001 (2010): 145–158. <a href=\"https://doi.org/10.1159/000272059\">https://doi.org/10.1159/000272059</a>.","ieee":"R. Huber <i>et al.</i>, “Functional Characterization of a Partial Loss-of-Function Mutation of the Epithelial Sodium Channel (ENaC) Associated with Atypical Cystic Fibrosis,” <i>Cellular Physiology and Biochemistry</i>, vol. 25, no. 001, pp. 145–158, 2010, doi: <a href=\"https://doi.org/10.1159/000272059\">10.1159/000272059</a>.","apa":"Huber, R., Krueger, B., Diakov, A., Korbmacher, J., Haerteis, S., Einsiedel, J., Gmeiner, P., Azad, A., Cuppens, H., Cassiman, J.-J., Korbmacher, C., &#38; Rauh, R. (2010). Functional Characterization of a Partial Loss-of-Function Mutation of the Epithelial Sodium Channel (ENaC) Associated with Atypical Cystic Fibrosis. <i>Cellular Physiology and Biochemistry</i>, <i>25</i>(001), 145–158. <a href=\"https://doi.org/10.1159/000272059\">https://doi.org/10.1159/000272059</a>"},"_id":"54942","author":[{"last_name":"Huber","full_name":"Huber, Regina","first_name":"Regina"},{"full_name":"Krueger, Bettina","last_name":"Krueger","id":"49428","orcid":"0000-0001-5351-1785","first_name":"Bettina"},{"first_name":"Alexei","last_name":"Diakov","full_name":"Diakov, Alexei"},{"first_name":"Judit","last_name":"Korbmacher","full_name":"Korbmacher, Judit"},{"full_name":"Haerteis, Silke","last_name":"Haerteis","first_name":"Silke"},{"last_name":"Einsiedel","full_name":"Einsiedel, Jürgen","first_name":"Jürgen"},{"last_name":"Gmeiner","full_name":"Gmeiner, Peter","first_name":"Peter"},{"first_name":"Abul","last_name":"Azad","full_name":"Azad, Abul"},{"last_name":"Cuppens","full_name":"Cuppens, Harry","first_name":"Harry"},{"first_name":"Jean-Jaques","last_name":"Cassiman","full_name":"Cassiman, Jean-Jaques"},{"full_name":"Korbmacher, Christoph","last_name":"Korbmacher","first_name":"Christoph"},{"first_name":"Robert","last_name":"Rauh","full_name":"Rauh, Robert"}],"user_id":"49428","type":"journal_article","department":[{"_id":"35"},{"_id":"22"}],"language":[{"iso":"eng"}],"publisher":"S. Karger AG","title":"Functional Characterization of a Partial Loss-of-Function Mutation of the Epithelial Sodium Channel (ENaC) Associated with Atypical Cystic Fibrosis","year":"2010","issue":"001","volume":25}