Lets face it, grapes are irresistible; at least humans seem to think so. But some birds are less sure. Bruce Bryant explains that methyl anthranilate in grape skins is so unpleasant to birds that a dose is enough to trigger vigorous head shaking `in an effort to rid themselves of the offensive substance'. But how methyl anthranilate inflicts pain on its feathered victims wasn't clear, until Bruce Bryant and his colleagues at the Monell Chemical Senses Center began teasing apart the cellular mechanisms of pain transduction in chicken neurons (p. 715)

Bryant explains that all creatures have a well-developed suite of defensive senses that detect danger, called nociceptors. Nociceptors from the head signal painful encounters with irritants via the trigeminal ganglion,and methyl anthranilate is no exception. Bryant and his colleagues Michael Kurnellas and Michael Kirifides were keen to get to the molecular mechanisms of the painful message, so they began tracing how the neurons registered an encounter with methyl anthranilate.

First Kirifides began mapping the neurone's concentration response, by increasing the cell's methyl anthranilate exposure from 10 to 300 μmol l–1, and watched their calcium levels rise. The cells reached a peak at 300 μmol l–1 methyl anthranilate. `In the pain field these levels [of methyl anthranilate] are very high' explains Bryant,`but not unrealistic'. And when the team tested the proportion of cells that responded to methyl anthranilate, they found that almost 50% of trigeminal neurons responded to the irritant.

But what was the molecular mechanism of the painful encounter? The team decided to investigate calcium signalling in the neurones by starving the cells of calcium and tracking their response to the irritant. Bryant explains that the neurone's calcium signal originates from one of two sources, either calcium stores within the cell or an extracellular source, so the team removed the extracellular source of calcium and tested the cells' response to methyl anthranilate. If the signal's calcium originated from reserves in the cell,the cell could still respond to methyl anthranilate, but if external calcium was necessary for the neurone's signal, removing it would abolish the signal. There was no response. Methyl anthranilate was stimulating the neurone's calcium uptake, but how was it getting in?

Bryant knew that some calcium uptake channels are activated by voltage changes across the neurone, sometimes caused by sodium uptake, so the team decided to test whether a voltage gated channel was involved in the bird's aversion response by removing sodium from the fluid bathing the cells and treating them with methyl anthranilate. Again the cells failed to respond to the irritant. Bryant realised that sodium entry into the cell changes the membrane's potential and activates the calcium channel, to mediate the bird's painful experience.

But why are Bryant, Larry Clark and the US Department of Agriculture intrigued by avian aversion to certain flavours? `Up to 5% of cattle feed is eaten by birds' Bryant explains, which can amount to significant losses for a farmer afflicted by a hungry flock. Bryant and Clark hope that if they can understand how foul tastes, that mammals barely notice, affect birds it might be possible to design non-lethal repellents that drive the feathered pests away, leaving cattle to dine, unaccosted.

Kirifides, M. L., Kurnellas, M. P., Clark, L. and Bryant, B. P. (
). Calcium responses of chicken trigeminal ganglion neurons to methyl anthranilate and capsaicin.
J. Exp. Biol.