Defense Date

2018

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Vijay Lyall

Abstract

ENaC is a constitutively open heterotrimeric channel which regulates Na+ transport in tight epithelia of the kidney, lungs, colon and anterior tongue containing fungiform taste buds. The amiloride-sensitive ENaC is comprised of aβg subunits. Humans express an additional subunit, the d subunit. Therefore, humans contain both aβg-ENaC and dβg-ENaC functional channels. Relative to aβg-ENaC, the dβg-ENaC is 10-fold less sensitive to amiloride. In the mammalian anterior tongue, ENaC is expressed in fungiform salt sensing taste receptor cells and is the Na+-specific salt taste receptor. In mammals, salt elicits an inverted U shaped behavioral response. Lower concentrations of salt are appetitive while high salt concentrations are aversive. The appetitive salt concentrations are sensed via ENaC. Thus, modulating ENaC activity in fungiform taste receptor cells will, in turn, regulate salt intake. The aim of this project is to investigate the effect of a common food ingredient, capsaicin, on ENaC expression and function in two cell lines, HEK293 cells and cultured adult human fungiform taste bud cells (HBO cells). Capsaicin, a TRPV1 agonist was chosen because in previous studies, it modulated chorda tympani taste nerve responses to NaCl in a dose-dependent manner. Most importantly, capsaicin and other agonists of TRPV1 were effective in modulating human salt taste perception. It is likely that the effect of capsaicin is due to its interactions with TRPV1, because TRPV1 and ENaC subunits are co-expressed in cortical collecting duct cells (CCD) and in a subset of human taste bud cells. In support of this hypothesis, TRPV1 has been shown to regulate ENaC expression and function in CCD cells of rats and mice. Using immunohistochemical techniques, our results demonstrate that TRPV1 is co-localized with the d-ENaC subunit in HBO cells. Additionally, the results in HEK-293 cells suggest that the activation of TRPV1 via capsaicin has a modulatory effect on d-ENaC mRNA and protein expression as well ENaC channel function measured as Na+ flux.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

7-12-2018

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