Investigating the Putative Activation Gate in the Selectivity Filter of the TRPV1 Channel

The TRPV1 cation channel functions as heat sensor and an integrator of painful stimuli in sensory neurons. The mechanism through which any of the multiple known TRPV1 modulators induce the opening and closing of the pore is unknown. In order to understand this, it is necessary to identify the regions of the channel that directly open and close the pore, known as “activation gates”. CryoEM structures of the TRPV1 channel in different closed and activated states revealed that the conduction pathway in the closed state presents two constrictions, or activation gates, that have to expand in the activated state to enable cation conduction.