▁this ▁ion ▁and ▁functional ▁studies ▁demonstrated ▁that ▁this ▁site ▁controls ▁the ▁various ▁different ▁effects ▁of ▁calci um ▁on ▁the ▁channel -- nam ely ▁pot enti ation , ▁des ens it ization , ▁and ▁re ceptor - operation . ▁ ▁C lin ical ▁significance ▁ ▁In ▁ 2 0 0 8 , ▁it ▁was ▁observed ▁that ▁c aff e ine ▁suppress es ▁activity ▁of ▁human ▁TR PA 1 , ▁but ▁it ▁was ▁found ▁that ▁mouse ▁TR PA 1 ▁channels ▁expressed ▁in ▁sens ory ▁neur ons ▁cause ▁an ▁a version ▁to ▁drink ing ▁c aff e ine - cont aining ▁water , ▁suggesting ▁that ▁the ▁TR PA 1 ▁channels ▁medi ate ▁the ▁per ception ▁of ▁c aff e ine . ▁ ▁TR PA 1 ▁has ▁also ▁been ▁imp licated ▁in ▁air way ▁ir rit ation ▁by ▁cig aret te ▁smoke , ▁clean ing ▁supplies ▁and ▁in ▁the ▁skin ▁ir rit ation ▁experienced ▁by ▁some ▁sm ok ers ▁trying ▁to ▁quit ▁by ▁using ▁nic ot ine ▁replacement ▁ther ap ies ▁such ▁as ▁in hal ers , ▁sp ray s , ▁or ▁patch es . ▁A ▁miss ense ▁mut ation ▁of ▁TR PA 1 ▁was ▁found ▁to ▁be ▁the ▁cause ▁of ▁a ▁her edit ary ▁epis od ic ▁pain ▁synd rome . ▁A ▁family ▁from ▁Colombia ▁suff ers ▁from ▁" deb il it ating ▁upper - body ▁pain ▁starting ▁in ▁inf ancy " ▁that ▁is ▁" us ually ▁triggered ▁by ▁fast ing ▁or ▁fat igue ▁( ill ness , ▁cold ▁temperature , ▁and ▁physical ▁ex ert ion