The capsaicin receptor, a true polymodal sensory receptor molecule. A. Schematic representation of the topology of a TRPV1 protein subunit. The functional channel is a tetramer formed by the ensemble of four such subunits. Marked in orange are residues influencing capsaicin binding. Marked in blue are two extracellular residues critical for activation by protons. The C-terminal region (shaded green) has been implicated in activation by heat but the critical residues are still unknown. B. Whole-cell I-V relationships of a HEK293 cell transfected with rat TRPV1 showing the activation of currents by low pH (6.0), heat (42°C) and capsaicin (100 nM) (A. Mälkiä, unpublished).