With the right stimulation, an ion channel changes its stripes, say Man-Kyo Chung, Ali Guler, and Michael Caterina (Johns Hopkins School of Medicine, Baltimore, MD).

Even ion channels that are a little promiscuous have their favorite passengers. Such channels were generally thought to stay true to their preferred customers. But Chung et al. found that the TRPV1 channel of pain-sensing neurons was more fickle.

TRPV1 opens its gates when it binds to the chili pepper compound, capsaicin. The new electrophysiology experiments showed that, upon first opening, the channel mostly let through small cations, such as calcium and sodium. But over time, the channel became more permissive to larger cations.

The channel also tweaked its preference for calcium over sodium. When extracellular calcium levels were high, the channel's preference for calcium waned with time. But if calcium levels were low, its calcium preference further increased.

The alterations probably stem from structural changes upon capsaicin binding. Heat and camphor also open the channel, but they did not have such a strong effect on passenger preferences. TRPV1 phosphorylation, by contrast, amplified the selectivity changes. “This is another layer at which the details of ionic flux into the cell can be regulated,” says Caterina. It is not clear, however, which large cations that might enter through TRPV1, such as spermidine, are physiologically relevant to neurons.

Chung, M.-K., et al.
Nat. Neurosci.