Sodium chloride—once dissociated into ions (individual atoms that carry an electrical charge)—imparts salt taste. It is now widely accepted that it is the sodium ion (Na+) that is primarily responsible for saltiness, although the chloride ion (Cl−) plays a modulatory role (Bartoshuk, 1980). For example, as the negatively charged ion (anion) increases in size (e.g., from chloride to acetate or gluconate), the saltiness declines. Many sodium compounds are not only salty but also bitter; with some anions, the bitterness predominates to such a degree that all saltiness disappears (Murphy et al., 1981).
It is believed that there are two or more types of receptors in the oral cavity, primarily on the tongue, that are responsible for triggering salt tastes (Bachmanov and Beauchamp, 2007), but major gaps in the understanding of salt taste reception remain. The most prominent hypothesis, which has been demonstrated in mice and rats, is that one set of receptors playing a role in salt taste perception involves ion channels or pores (Epithelial sodium [Na] Channels: ENaCs). ENaCs allow primarily sodium (and lithium) to move from outside the taste receptor cell, where it has been dissolved in saliva, into the taste cell. The resulting increase in Na+ inside the taste cell causes the release of neurotransmitters that eventually signal salt taste to the brain (Chandrashekar et al., 2010; McCaughey, 2007; McCaughey and Scott, 1998) (Figure 3-4). Because sodium and lithium are the only ions known to produce a purely salt taste, it is believed that these sodium-and lithium-specific channel receptors play a major role in sensing saltiness (Beauchamp and Stein, 2008; McCaughey, 2007).
The body of evidence supporting sodium channel receptors as salt taste receptors is based largely on animal models, primarily rodents. These findings indicate that the diuretic compound amiloride, a molecule that blocks sodium channels, reduces salt taste perception in these animals. In humans, however, amiloride is much less effective in blocking salt taste perception (Halpern, 1998). Nevertheless, since human salt taste mechanisms are highly unlikely to differ in fundamental ways from those of rodents, most investigators are convinced that an ENaC is the most likely receptor in humans as well. If this hypothesis is correct, it has profound implications for the search for salt substitutes. Given the specificity of this channel for sodium, it is highly unlikely that any substance could fully replace sodium (with the exception of lithium, which is unacceptable because it is highly toxic).
At least one other type of taste receptor that detects sodium chloride and some other salts is thought to exist. The hypothesis for a second receptor is based in part on work showing that some salt taste is perceived even when cations that cannot fit into the ENaC (potassium, calcium, am-