TRPA1 as a O₂ sensor detects microenvironmental hypoxia in the mice anterior cingulate cortex

Transient receptor potential ankyrin 1 (TRPA1) is a member of the TRP channel family and is expressed in peripheral and central nervous systems. In the periphery, TRPA1 senses cold and pain. However, the functions of TRPA1 in the CNS are unclear. Here, we examined the roles of TRPA1 on neural activity and synaptic transmission in layer II/III pyramidal neurons from mice anterior cingulate cortex (ACC) by whole-cell patch-clamp recordings. The activation of Cinnamaldehyde (CA), which is TRPA1 agonist produced inward currents and these were blocked by the TRPA1 antagonists. Furthermore, activating TRPA1 changed the properties of action potentials such as the firing rate, rise time and decay time. In contrast, stimulating TRPA1 did not alter the spontaneous synaptic transmission. Finally, we examined the functional role of TRPA1 on neurons in a hypoxic environment. We induced an acute hypoxia by substituting nitrogen (N₂) gas for oxygen (O₂) in the external solution. N₂ produced biphasic effects that consisting of inward currents in the early phase and outward currents in the late phase. Importantly, blocking TRPA1 reduced inward currents, but not outward currents. In contrast, a K_ATP channel blocker completely inhibited outward currents. These results suggest that TRPA1 acts on postsynaptic neurons in the ACC as an acute O₂ sensor.