Salt-Evoked Lingual Surface Potential in Humans

Abstract

. Salt sensing in animals involves the epithelial sodium channel (ENaC). If ENaC were involved in human salt sensing, then the lingual surface potential (LSP) would hyperpolarize when exposed to sodium. We developed a chamber to measure the LSP while different solutions superfused the surface of the tongue and a technique to adjust for the junction potentials induced by varying salt concentrations. Changing the superfusion solution from rinse solution (30 mM KCl) to 300 mM NaCl (ϩ30 mM KCl) caused the LSP to hyperpolarize by 10.1 Ϯ 0.7 mV (n ϭ 13, P Ͻ 0.001). With repeated challenge the LSP response was reproducible. Increasing the Na concentration from 100 to 600 mM increased hyperpolarization by 35 Ϯ 4.8% (n ϭ 9, P Ͻ 0.001). To examine whether amiloride affects the LSP, 0.1 mM amiloride was added to 300 mM NaCl; it reduced the hyperpolarization by 18.5 Ϯ 4.3% (P Ͻ 0.005, n ϭ 11). However, the amiloride effect was not uniform: in six volunteers, amiloride inhibited the LSP by as much as 42%, while in five subjects, amiloride inhibited Ͻ5% of the LSP. In an amiloride sensitive volunteer, amiloride exerted 50% of its effect at 1 M. In conclusion, we have demonstrated that the LSP can be measured in humans, that Na hyperpolarizes the LSP, that increasing the Na concentration increases LSP hyperpolarization, and that amiloride inhibits the Na evoked LSP in some humans. While ENaC is involved in sensing salt, its role appears to vary among individuals.

Influence of temperature on taste perception

“…This contrasts sharply with the observations in rodents, where the contribution of ENaC to salty taste transduction is much stronger [25,29]. Notably, the amiloride sensitivity of salt-evoked lingual surface potentials seems to vary significantly among humans, suggestive of inter-individual differences in the contribution of ENaC to salt sensing [30]. Considering that ENaC expression in taste tissue and salty taste responses can be altered by dietary conditions through hormonal regulation [31], it would be interesting to test whether the amiloridesensitive component of the response to NaCl is larger in Na + -depleted human subjects and if this influences the cold stimulation of salty taste.…”

“…Interestingly, the gustatory nerve response to NaCl in rats and mice contains amiloride-sensitive components that are enhanced either by cold (LT, low-temperature component) or heat (HT, high-temperature component) [14,32]. Notably, there is a differential expression of temperature-dependent and temperature-independent amiloridesensitive components in several murine strains [32], which may echo the large inter-individual variability in the amiloride sensitivity of human responses to salt [30]. Later identification of LT and HT single chorda tympani fibres suggests the existence of amiloride-sensitive salt receptors with different temperature sensitivities [33].…”

A Role of the Epithelial Sodium Channel in Human Salt Taste Transduction?

“…As seen for α-ENaC, functional expression in vitro of the δ-subunit is increased when it is co-expressed with β-and γ-ENaC (Waldmann et al 1995). Subunit composition may also affect the sensitivity towards amiloride (Ji et al 2006) and contribute to the debate of amiloride sensitivity of salty taste in humans (Tennissen 1992;Ossebaard and Smith 1995;Smith and van der Klaauw 1995;Tennissen and McCutcheon 1996;Anand and Zuniga 1997;Halpern and Darlington 1998;Feldman et al 2003).…”

ENaCs and ASICs as therapeutic targets

“…In mice, knocking out the conductive ␣ENaC subunit from taste receptor cells abolished the sodium taste response (76). However, the effect of amiloride to block salt taste is not uniform, which may be explained by the presence of single nucleotide polymorphisms in the primary sequence of ␣ENaC (127,348). These studies suggest that a small-molecule potentiator or activator of ENaC (256) could help with adherence to a low-salt diet, by helping recreate the sensation of higher sodium intake through manipulation of the channel.…”