Glutamate in unusual places

Glutamate in unusual places lutamate has a critical physiological function unrelated to its job as a neurotransmitter, according to results from M.M. Reddy and Paul Quinton (University of California, San Diego, CA). The duo find that glutamate activates an epithelial ion channel that is mutated in patients with cystic fibrosis. Cystic fibrosis is caused by mutations in the CFTR anion channel, which is found in various epithelial tissues, including the lungs. A long-standing assumption that CFTR is activated by phosphorylation and ATP has recently been challenged by observations that the channel is open regardless of kinase activity in sweat glands. Epithelial cells, including sweat glands, seem to express glutamate receptors, although their function is not known. Reddy studied the effect of glutamate on epithelial transport and found that it activated CFTR. CFTR is activated by glutamate only from the cytoplasmic side, however, and thus is distinguished from standard glutamate receptors, which respond to extracellular glutamate. Reddy does not yet know whether glutamate binds to CFTR directly or activates it indirectly. Cl may not be the only CFTR-conducted ion important for normal gland function. Reddy found that bicarbonate ions also passed through the CFTR channel in the presence of both glutamate and ATP. Mutant versions of CFTR found in patients with severe forms of cystic fibrosis were deficient in both Cl and bicarbonate transport. Milder CFTR mutations spared bicarbonate transport. The findings suggest that defects in bicarbonate transport should not be ignored in the search for treatments for cystic fibrosis.