The very small-conductance K+ channel K(V)LQT1 and epithelial function

K(V)LQT1 (KCNQ1) is a very small conductance K+ channel distributed widely in epithelial and non-epithelial tissues. Its specific biophysical and phar macological properties are determined by the regulatory subunits I-sK (KCNE 1) and MiRP2 (KCNE3). In epithelial cells of the inner ear, pancreas, and a irways it interacts with I-sK to conduct a voltage-gated and slowly activat ing K+ current. In the colon it coassembles with KCNE3 to conduct an instan taneous and constitutively active K+ current. In Cl- secretory epithelia, s uch as the colon and pancreas, this K+ channel provides the driving force f or Cl- exit and is located in the basolateral membrane. In the inner ear it enables luminal secretion of K+ into the endolymphatic space. The function al relevance of K(V)LQT1 to epithelial function is revealed by blocking it pharmacologically or by studying animals with a genetic defect for it, whic h result in the breakdown of colonic Cl- secretion and endolymph production , respectively. K(V)LQT1 K+ channels are activated via cAMP or Ca2+ and inh ibited by the chromanol 293B. Interaction with as yet unknown regulatory su bunits may determine the properties of K(V)LQT1 in the rectal gland and oth er epithelial tissues in which K(V)LQT1 is not inhibited by chromanols.