Research of the Althaus laboratory focuses on the molecular physiology of epithelial ion channels and transport proteins in vertebrates. The work ranges from basic research on the function and regulation of epithelial ion channels and transporters in animals, up to translational aspects in Biomedicine and Pharmacology. We are combining electrophysiological techniques for the analysis of single ion channels, cells, and epithelial tissues, with molecular biological/biochemical methods and photochemistry.
Molecular ion channel physiology
We are currently investigating the molecular composition as well as functional regulation of the epithelial sodium channel (ENaC) invertebrates. NICs are sodium selective ion channels that are found in various vertebrate epithelia (e.g. renal epithelia, respiratory epithelia, or sweat glands) and are important for the control of salt and water homeostasis.
We are investigating cellular signaling mechanisms regulating ENaC activity in epithelial cells and study how the molecular subunit composition of this ion channel determines its regulation and physiology. Furthermore, our collaborators and we are developing novel pharmacological tools in order to modulate the activity of this ion channel.
Controlling epithelial sodium channels with light using photoswitchable amiloride.
Schönberger M, Althaus M, Fronius M, Clauss W, Trauner D.
Nature Chemistry. 2014; 6(8):712-9
Mechano-sensitivity of epithelial sodium channels (ENaCs): laminar shear stress increases ion channel open probability.
Althaus M, Bogdan R, Clauss WG, Fronius M.
FASEB J. 2007; (10):2389-99
Evolution of ion channels in vertebrates
Using a comparative physiological approach, we are currently investigating how ion channels which are important for salt and water conservation emerged during fish-tetrapod evolution. We are particularly interested in how selective pressure during water-land transition of tetrapod ancestors determined the molecular physiology of epithelial ion channels.
Wichmann L, Dulai JS, Marles-Wright J, Maxeiner S, Szczesniak PP, Manzini I, Althaus M.
An extracellular acidic cleft confers profound H+-sensitivity to epithelial sodium channels containing the δ-subunit in Xenopus laevis.
Journal of Biological Chemistry 2019. In press.
Incorporation of the delta-subunit into the epithelial sodium channel (ENaC) generates protease-resistant ENaCs in Xenopus laevis.
Wichmann L, Vowinkel KS, Perniss A, Manzini I, Althaus M.
Journal of Biological Chemistry. 2018; doi:10.1074/jbc.RA118.002543
Epithelial ion transport physiology
In epithelial cells, the concerted action of ion channels and transporters controls the transport of electrolytes across the epithelium and thereby osmotically facilitates the absorption and secretion of liquid. In the lung, these transepithelial ion transport processes determine the volume and composition of a thin liquid layer lining the respiratory epithelium. A precise volume regulation of this liquid layer is critical for normal lung function.
Dehydration of the epithelium in the airways impairs mucus clearance and can lead to chronic lung infection, whereas excess liquid in the distal lung can lead to the formation of pulmonary oedema and impaired gas exchange. We are investigating the cellular mechanisms which regulate ion transport processes in respiratory epithelia and how their malfunction contributes to the development of lung diseases.
Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption.
Krause NC, Kutsche HS, Santangelo F, DeLeon ER, Dittrich NP, Olson KR, Althaus M.
Am J Physiol Regul Integr Comp Physiol. 2016; 311(3):R607-17
ENaC inhibitors and airway re-hydration in cystic fibrosis: state of the art.
Curr Mol Pharmacol. 2013; 6(1):3-12
The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells.
Althaus M, Urness KD, Clauss WG, Baines DL, Fronius M.
Br J Pharmacol. 2012; 166(6):1946-63