the trpm8 channel is a homotetramer, composed of four identical subunits with a transmembrane domain with six helices (s1–6). the first four, s1–4, act as the voltage sensor and allow binding of menthol, icilin and similar channel agonists. s5 and s6 and a connecting loop, also part of the structure, make up the pore, a non-selective cation channel which consists of a highly conserved hydrophobic region, a range of diverse components are required for the high level of specificity in responding to result in ion flow to cold and menthol stimuli.