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 neurons. Thus, we propose that cold sensitivity of TRPA1 is indirect and is dependent on cellular context. © 2009 Caspani and Heppenstall.