Selectivity and Characterization of the Permeant Ion Effect in the Rapidtransitions on the Pore of TRPV1 Channel

Abstract

The transient receptor potential vanilloid 1 (TRPV1) channel can be activated by stimuli such as capsaicin, pH <5.4, heat and voltage. Its structure is similar to voltage-dependent potassium channels, but in contrast the mechanism voltage detection has remained unknown.TRPV1 is classified as a non-selective cation channel with more permeability to divalent ions as calcium. We characterized the selectivity of TRPV1 through inside-out patch clamp recordings in cells HEK293. We find a selectivity sequence for monovalent ions: Cs+ ≈ NH4+ > Rb+ ≈ K+ > Na+ > Li+. Additionally, we find that, in single-channels recordings, there are rapid fluctuations on the current that occur during the open state of the channel. These fluctuations are observed as an asymmetric tail in the all-points current amplitude histograms. This asymmetry increases at positive voltages and varies depending on the permeant ion. These fluctuations can be explained by rapid transition between the open state and several closed states. The lifetime of the open state is related to the type of ion that occupies the channel pore. Amplitude histograms are analyzed with through simulation of histograms resulting from several models considering one open state and two or more closed states with appropriate transition rate constants. These experiments indicate that the selectivity filter undergoes rapid transitions that might be related to gating and might reflect the movement of a selectivity filter gate. seems to occur in the selectivity filter. Supported by grants DGAPA-PAPIIT: IN203318 and CONACYT: 252644.