Permeant cations modulate pore dynamics and gating of TRPV1 ion channels

TRPV1 ion channels are important players in thermal and chemical sensation and have roles in pathological states. In this work, Garcia-avila et al. employ single-channel recordings to observe that large cations are more permeable than smaller ones and uncover fast conformational changes that are distinctly modulated by the cation occupying the pore. The transient receptor vanilloid 1 (TRPV1) is a non-selective ion channel, which is activated by several chemical ligands and heat. We have previously shown that activation of TRPV1 by different ligands results in single-channel openings with different conductance, suggesting that the selectivity filter is highly dynamic. TRPV1 is weakly voltage dependent; here, we sought to explore whether the permeation of different monovalent ions could influence the voltage dependence of this ion channel. By using single-channel recordings, we show that TRPV1 channels undergo rapid transitions to closed states that are directly connected to the open state, which may result from structural fluctuations of their selectivity filter. Moreover, we demonstrate that the rates of these transitions are influenced by the permeant ion, suggesting that ion permeation regulates the voltage dependence of these channels. Our data could be the basis for more detailed MD simulations exploring the permeation mechanism and how the occupancy of different ions alters the three-dimensional structure of the pore of TRPV1 channels.

Automated summary

TRPV1 ion channels play important roles in thermal and chemical sensation, as well as in pathological states. This study reveals that large cations are more permeable than smaller ones and uncovers fast conformational changes modulated by the cation occupying the pore. The findings also demonstrate that ion permeation influences the voltage dependence of TRPV1 channels.