Mutated fruit flies bypass the salt. (A Matter of Taste).

People's fondness for salty snacks reflects a fundamental biological imperative. "All cells, in order to survive, need salt," says Lei Liu of the Howard Hughes Medical Institute at the University of Iowa in Iowa City. To keep themselves supplied with this critical nutrient, animals have developed ways for sensing sodium chloride and other salts.

By creating mutant fruit flies with an impaired capacity to taste salt, Liu and his colleagues have now identified several genes that contribute to this crucial sensory system in insects. Liu suggests that the fly research could provide insights into how people taste salt. It may even lead to an effective salt substitute to fight high blood pressure and other conditions exacerbated by today's salt-rich diets, he speculates.

When it comes to salt, the fruit fly Drosophila melanogaster acts much like a person. Food or water sources with too much salt repel the flies, but those with low concentrations attract them. The flies can even distinguish between sodium chloride, which is typical table salt, and potassium chloride, which tastes even saltier to people.

To investigate how flies sense salt, Liu and his colleagues drew upon past work indicating that certain cellular pores, known as epithelial sodium channels, act as salt receptors in mammals. These pores, through which sodium ions flow into cells, are found on rodents' taste buds, for example.

Yet not all biologists are convinced that this sodium channel is a widespread salt-sensing receptor. For one thing, even though the sodium-channel-blocking drug amiloride impairs salt taste in rodents and some other animals, this effect isn't consistent among all species or even among different strains of rodents. Moreover, no one has shown clearly that the human tongue has this particular sodium channel, notes Sue C. Kinnamon of Colorado State University in Fort Collins.

Scientists sometimes investigate the role of an ion channel by inactivating the genes encoding the channel's protein constituents. In mice, however, this particular sodium channel appears to do more than mediate salt taste. Mice lacking the channel die as embryos or just after birth.

Seeking to do a similar gene-knockout experiment in fruit flies, Liu and his colleagues identified insect genes that closely resemble the mammalian ones that encode the subunits of the epithelial sodium channel. Some of these fly genes are active in taste-sensing tissues of larvae and in the taste-sensing bristles of the adult insect, Liu's group reports in the July 3 Neuron.

The investigators inactivated several of the insect genes and tested the salt perception of the resulting mutant insects. Both as larvae and adults, the flies are equally attracted to pure water and water containing low concentrations of salt, Liu and his colleagues found. Unlike typical flies, the mutant insects can't distinguish between sodium chloride and potassium chloride.

"We see a very clear salt-taste defect," says Liu.

This is the first time that gene-knockout techniques have been used to establish a component of the salt-sensing pathway in any species, says Kinnamon. Even so, she cautions, the epithelial sodium channel may not be relevant to human salt perception.

"The salt receptor is going to be different in different species," Kinnamon says. "It might be related [to this channel] in humans, but it might not be."