The transient receptor potential (TRP) ion channels are a family of channels expressed in many cell and tissue types that allow the influx of calcium ions into cells. Little is known about their physiological function, although a role in the detection or transduction of sensory stimuli, including changes in temperature, has been suggested. Reporting in Neuron, Chuang et al. show that for some TRP channels to be maximally effective, two or more physiological stimuli must be present at the same time, indicating that they function as coincidence detectors.

One TRP channel, TRPM8, is sensitive to a reduction in ambient temperature. In response to cold, TRPM8 depolarizes afferent nerve fibres in the somatosensory system, which induces psychophysical sensations of cold. TRPM8 channels are also gated by natural cooling agents, such as menthol, and by synthetic 'super-cooling agents', such as icilin, which is not structurally related to menthol. These agonists modulate the temperature threshold at which TRPM8 channels can be activated, so that they open at higher than normal temperatures.

However, it seems that these two cooling agents work by different mechanisms. TRPM8 is rapidly activated in response to the single stimulus menthol in the absence of calcium ions. By contrast, as Chuang et al. show using electrophysiological techniques, full activation of TRPM8 channels by icilin occurs only with simultaneous exposure to intracellular calcium ions. Calcium ions alone apparently have no such effect on TRPM8 channels, and work only in conjunction with icilin.

The need for two independent agonists to be present simultaneously for full activation of TRPM8 channels, and their permeability to calcium ions, could allow TRPM8 to modulate its gating activity according to the concentration of icilin or similar agonists and the presence of another stimulus that promotes an increase in intracellular calcium. This, in turn, might allow cells to fine-tune their sensitivity to a specific chemical stimulus and to increase the range of environmental signals to which they are sensitive — a property that is especially useful for channels involved in the transduction of sensory stimuli.