Heat and Capsaicin Activate TRPV1 Channels to Different Open States

Both heat and capsaicin can strongly activate TRPV1 channels. However, the underlying mechanism by which the activation gate responds to these two distinct stimuli is unknown.We use single-channel recordings of the wildtype and mutant TRPV1 channels with large unitary conductance to compare channel activation driven by each of the gating modalities. As shown in the figure, the heat-induced openings (top trace) exhibit much shorter open times than those of ligand-induced channel openings (bottom trace). In addition, we observe that at saturating concentrations capsaicin can only partially open TRPV1 channels. Raising temperature in the presence of capsaicin leads to an increase in open probability.These results demonstrate that heat and capsaicin gate the channel to different open states, suggesting that they do not share the same activation pathway.View Large Image | View Hi-Res Image | Download PowerPoint Slide