Hobbling neuron receptors

Efforts to determine the roles of two related neuronal receptors should get a boost from recent discoveries at the University of California, San Francisco. Glutamate-activated ion channels known as AMPA receptors play a central role in processes related to learning and memory. But attempts to differentiate between the functions of two types of these receptors have produced conflicting results so far. A better handle on the receptors' behavior should be forthcoming now that Aaron Nilsen and Pamela M. England have found that philanthotoxin-7,4 (shown) selectively inhibits the activity of just one of the receptor types (J. Am. Chem. Soc. 2007, 129, 4902). The UCSF duo determined that differences in the carboxyl ends of subunits within the two receptors give rise to overall structural differences that affect the receptors' relative affinity for the inhibitor. Nilsen and England's approach to synthesizing the compound—an analog of a wasp venom toxin—more than doubles the yield previously achieved by another research group.