Epithelial Na+ Channel (ENaC) Formed by One or Two Subunits Forms Functional Channels That Respond to Shear Force

Frontiers in Physiology, vol. 11, pp. 141

Abstract

Canonical epithelial sodium channels (ENaCs) are heterotrimers formed by α, β and ɣ ENaC subunits in vertebrates and belong to the Degenerin/ENaC family of proteins. Proteins from this family form mechanosensitive channels throughout the animal kingdom. Activity of canonical ENaC is regulated by shear force (SF) mediating Na+ absorption in the kidney and vascular tone of arteries. Expression analysis suggests that non-canonical ENaC, formed by single or only two subunits, exist in certain tissues, but it is unknown if these channels respond to SF. α, β ɣ, and  ENaC subunits were expressed either alone or in combinations of two subunits in Xenopus oocytes. Amiloride-sensitive currents and the responses to SF were assessed using two-electrode voltage clamp recordings. With the exception of ɣ ENaC all homomeric channels provided amiloride-sensitive currents and responded to SF applied via a fluid stream directed onto the oocytes. Channels containing two subunits were also activated by SF. Here the presence of the ɣ ENaC subunit when co-expressed with α or δ augmented the SF response in comparison to the αβɣ/δβɣ ENaC. Overall we provide evidence that non-canonical ENaC can from channels that respond to SF. This supports a potential function of non-canonical ENaC as mechanosensors in epithelial, vascular, and sensory cells.

Authors 3

1. Jan-Peter Baldin

   University of Otago

   Affiliation as printed

   Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

2. Daniel Barth Aachen Institute of Physiology

   RWTH Aachen University

   Affiliation as printed

   Institute of Physiology, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany

3. Martin Fronius corresponding

   University of Otago

   Affiliation as printed

   Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

   HeartOtago, University of Otago, Dunedin, New Zealand