TRPA1 and Cold Transduction: An Unresolved Issue?

TRPA1 was originally characterized as a cold-activated ion channel; however, since the initial description there has been some disagreement about its role in cold sensation. Here, we review the literature on the function of TRPA1 as a cold sensor. Many studies have demonstrated that TRPA1 can be activated by cold when expressed in heterologous systems, but its role as a cold sensor in native peripheral sensory neurons remains uncertain. We argue that TRPA1 is activated indirectly by cold via a background Ca 2+ infl ux seen in cells during cooling. This background cold response is present in most heterologous cell types, but not in sensory neu-rons. Thus, we propose that cold sensitivity of TRPA1 is indirect and is dependent on cellular context.