Epithelial cells are exposed to a variety of mechanical forces, but little is known about the impact of these forces on epithelial ion channels. Here we show that mechanical activation of epithelial sodium channels (ENaCs), which are essential for electrolyte and water balance, occurs via an increased ion channel open probability. ENaC activity of heterologously expressed rat (rENaC) and Xenopus (xENaC) orthologs was measured by whole-cell as well as single-channel recordings. Laminar shear stress (LSS), producing shear forces in physiologically relevant ranges, was used to mechanically stimulate ENaCs and was able to activate ENaC currents in whole-cell recordings. Preceding pharmacological activation of rENaC with Zn2+ and xENaC with gadolinium and glibenclamide largely prevented LSS-activated currents. In contrast, proteolytic cleavage with trypsin potentiated the LSS effect on rENaC whereas the LSS effect on xENaC was reversed (inhibition of xENaC current). Further, we found that exposure of excised outside-out patches to LSS led to an increased ion channel open probability without affecting the number of active channels. We suggest that mechano-sensitivity of ENaC may represent a ubiquitous feature for the physiology of epithelia, providing a putative mechanism for coupling transepithelial Na+ reabsorption to luminal transport.
%0 Journal Article
%1 althaus_mechano-sensitivity_2007
%A Althaus, Mike
%A Bogdan, Roman
%A Clauss, Wolfgang G
%A Fronius, Martin
%D 2007
%J The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
%K Animals Biological_Transport Epithelial_Sodium_Channel Female Ion_Channel_Gating Mechanical Oocytes Patch-Clamp_Techniques Probability Rats Recombinant_Proteins Sodium Stress Xenopus_Proteins Xenopus_laevis
%P 2389-99
%R fj.06-7694com
%T Mechano-sensitivity of epithelial sodium channels (ENaCs): laminar shear stress increases ion channel open probability
%U http://www.ncbi.nlm.nih.gov/pubmed/17426066
%V 21
%X Epithelial cells are exposed to a variety of mechanical forces, but little is known about the impact of these forces on epithelial ion channels. Here we show that mechanical activation of epithelial sodium channels (ENaCs), which are essential for electrolyte and water balance, occurs via an increased ion channel open probability. ENaC activity of heterologously expressed rat (rENaC) and Xenopus (xENaC) orthologs was measured by whole-cell as well as single-channel recordings. Laminar shear stress (LSS), producing shear forces in physiologically relevant ranges, was used to mechanically stimulate ENaCs and was able to activate ENaC currents in whole-cell recordings. Preceding pharmacological activation of rENaC with Zn2+ and xENaC with gadolinium and glibenclamide largely prevented LSS-activated currents. In contrast, proteolytic cleavage with trypsin potentiated the LSS effect on rENaC whereas the LSS effect on xENaC was reversed (inhibition of xENaC current). Further, we found that exposure of excised outside-out patches to LSS led to an increased ion channel open probability without affecting the number of active channels. We suggest that mechano-sensitivity of ENaC may represent a ubiquitous feature for the physiology of epithelia, providing a putative mechanism for coupling transepithelial Na+ reabsorption to luminal transport.
@article{althaus_mechano-sensitivity_2007,
abstract = {Epithelial cells are exposed to a variety of mechanical forces, but little is known about the impact of these forces on epithelial ion channels. Here we show that mechanical activation of epithelial sodium channels (ENaCs), which are essential for electrolyte and water balance, occurs via an increased ion channel open probability. ENaC activity of heterologously expressed rat (rENaC) and Xenopus (xENaC) orthologs was measured by whole-cell as well as single-channel recordings. Laminar shear stress (LSS), producing shear forces in physiologically relevant ranges, was used to mechanically stimulate ENaCs and was able to activate ENaC currents in whole-cell recordings. Preceding pharmacological activation of rENaC with Zn2+ and xENaC with gadolinium and glibenclamide largely prevented LSS-activated currents. In contrast, proteolytic cleavage with trypsin potentiated the LSS effect on rENaC whereas the LSS effect on xENaC was reversed (inhibition of xENaC current). Further, we found that exposure of excised outside-out patches to LSS led to an increased ion channel open probability without affecting the number of active channels. We suggest that mechano-sensitivity of ENaC may represent a ubiquitous feature for the physiology of epithelia, providing a putative mechanism for coupling transepithelial Na+ reabsorption to luminal transport.},
added-at = {2008-12-12T16:43:23.000+0100},
author = {Althaus, Mike and Bogdan, Roman and Clauss, Wolfgang G and Fronius, Martin},
biburl = {https://www.bibsonomy.org/bibtex/21bf8aacfb15b1586f6ce4c240b01aeee/molcellphysio},
doi = {fj.06-7694com},
interhash = {a7fd1bb2a24972b9510e86588fa75913},
intrahash = {1bf8aacfb15b1586f6ce4c240b01aeee},
issn = {1530-6860},
journal = {The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology},
keywords = {Animals Biological_Transport Epithelial_Sodium_Channel Female Ion_Channel_Gating Mechanical Oocytes Patch-Clamp_Techniques Probability Rats Recombinant_Proteins Sodium Stress Xenopus_Proteins Xenopus_laevis},
month = {August},
note = {PMID: 17426066},
pages = {2389-99},
timestamp = {2008-12-13T10:41:58.000+0100},
title = {Mechano-sensitivity of epithelial sodium channels (ENaCs): laminar shear stress increases ion channel open probability},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17426066},
volume = 21,
year = 2007
}