Working with hamster cells driven to express VR-OAC, the researchers showed that VR-OAC is exquisitely sensitive to subtle changes in osmotic pressure. VR-OAC does not respond to changes in temperature, but it is "fine-tuned" by temperature, with maximum sensitivity at body temperature in mammals (37?C/98.6?F) and in birds (40?C/104?F).
"Our laboratories then began to characterize the properties of what we now know to be an osmotically gated channel," says Friedman. "These studies showed that, indeed, the channel opens in response to decreased salt concentration, or osmolarity. This opening admits a small amount of calcium, which in turn triggers the release of a burst of calcium from storage depots inside the cell. When this happens in key nerve cells in the brain's osmotic regulatory region, we suspect that these receptors would fire and produce a host of responses that affect thirst, salt intake and perhaps even salt excretion."
VR-OAC is a member of the new family of vanilloid receptor-related genes, which have several exciting functions, namely sensitivity to osmotic pressure, and possibly to mechanical stimuli, painful heat and to capsaicin, the pungent ingredient of hot peppers.
Liedtke's, Heller's, Hudspeth's and Friedman's co-authors are graduate student Yong Choe, Andrea M. Bell and Charlotte S. Denis in the Laboratory of Sensory Neuroscience; and postdoctoral associate Marc A. Mart-Renom, Ph.D., and Associate Professor Andrej Sali, Ph.D., head of a Laboratory of Molecular Biophysics, all at Rockefeller.