I love salt. It's just delicious. I wrote this post while noshing on deliciously salty popcorn, after a dinner which I put salt on. I crave salt so much that my parents used to joke about getting me a salt lick.
And I'm not alone. Sodium is an incredibly important part of life, which means it's also an important part of what we eat. To make sure we get enough salt, animals have evolved salt-sensing systems, and low levels (below 100 mM of NaCl) of salt are very attractive.
But there IS such a thing as too much salt. High levels of salt (>300 mM NaCl) are really aversive (from personal experience, I wonder if Carrabba's restaurant has concentrations of salt in their food over 300 mM). Most animals will quickly turn up their noses at a high salt concentration.
You probably know that you have classes of receptors on your tongue for taste (though they are not clustered into areas of your mouth, like front for sweetness, as previously thought). You have sweet, umami (savory), bitter, sour, and salt. In most animals, sweet and umami are always attractive, while bitter and sour are nasty (except where we have overcome the aversion to enjoy things like coffee and beer). Salt, though, is the only one that goes two ways, with low levels being attractive and high levels being aversive.
Now we know how low salt works. The salt receptors that are currently known are good for detecting low salt. But high salt, that's more difficult. First of all, our aversion to high salt concentrations is not very selective. While low salt detection is limited to good old NaCl, high salt detection is non-specific, working for many salts including NaCl, but others as well (like KCl).
Not only that, but if you block the low salt pathway (you can block the sodium channels involved by using a diuretic), the high salt pathway still functions, which means that there are other receptors involved. But what other receptors?
Well, it turns out that high salt is not just...salty. It's BITTER. and SOUR. Or at least, your receptors think so.
Oka et al. "High salt recruits aversive taste pathways" Nature, 2013.
How do you determine the high salt pathway? The authors first tyies the pharmacological method. You can find a pathway by trying to find what BLOCKS it. They did a survey of compounds and came up with one, allyl isothiocyanate (AITC). This is a chemical found in mustard oil.
You can see here some electrophysiological traces of the chorda tympani, the nerve that carries signals from the taste buds in the front of the tongue. It should be active in response to various chemical stimulants, like sugar, bitter, or, you know, salt.
And in response to high concentrations of salt, you can see on the top row that there's a strong response, the nerve has a large action potential. But in the presence of the mustard oil chemical AITC (in red), the action potentials are reduced. the AITC is blocking the high salt response.
But what is the AITC hitting? It's not hitting the low salt response (there was no change there). As you can see on the bottom row there, it's actually inhibiting the BITTER response.
So does high salt activate bitter receptors instead of salt ones? To examine this, the authors looked at the taste receptors themselves. They loaded bitter sensing cells (expressing the T2R receptor, which detects bitter) with calcium and added in expression of Green Flourescent Protein, so if the high salt was hitting bitter cells, they would see a flash of green.
And they definitely got it. You can see that high salt conditions as well as bitter cause a nice calcium induced glow in the bitter sensing cells. High salt hits bitter.
But when they continued to test in bitter-lacking knockout mice, they found that the bitter taste cells only account for about 50% of the high salt response. There is something else involved. But what? Well, if you're making a taste aversivem you've got two receptor types immediately available: bitter...and sour.
You can see in the second row here the nerves from mice lacking expression of sour receptors (TeNT). They also had a much lower response to high salt conditions (see the red peaks on the right?), about 50%.
So the bitter is 50%, the sour is 50%, what happens if you knock them both out?
Take a look at the bottom row of that image, you can see the nerves from a DOUBLE knockout, which doesn't express bitter or sour taste receptors. This one shows NO response to bitter, no response to sour...and no response to high salt, even though the low salt response is still there (though they also show no response to sweet and umami, which is interesting and possibly problematic).
But of course, these are all nerve recordings, these aren't salt behaviors. Does getting rid of these receptors change how animals respond to salt?
Here you can see measures of salt aversion and salt attraction, where animals are given increasing concentrations of salt, and you measure how much they lick at it. You can see that at lower concentrations (top panel), all the mice lick away, but as the concentration gets higher, most of the mice drop off. But the double knockout mouse stays put, completely unfazed by the high salt concentration. This is also expressed at the bottom of the figure in terms of salt attraction. As the salt concentration gets higher, normal mice show reduced attraction, but the double knockout mice show higher attraction. Without sour or bitter taste, high salt just tastes better and better.
This means that salt taste is a lot more wide-ranging than previously thought. Instead of just one receptor type, salt can activate three: salt at low concentrations, and bitter and sour at high concentrations. And it gives us some interesting insight into how salt can go from delicious to disgusting.
Oka, Y., Butnaru, M., von Buchholtz, L., Ryba, N., & Zuker, C. (2013). High salt recruits aversive taste pathways Nature DOI: 10.1038/nature11905