The role of potassium channels in excitable cells.

Potassium (K) channels regulate cellular excitability. Their opening hyperpolarises the membrane potential and induces quiescence whereas their closure produces depolarisation and excitation. One K-channel superfamily includes the delayed rectifier (KV), the A-type (KA) and the large conductance, Ca-sensitive (BKCa) channels. These serve to terminate excitatory events and consist of a tetramer of alpha-subunits each comprising six transmembrane-spanning segments including a voltage-sensor. Additional beta-subunits which modify inactivation and voltage sensitivity may also be present. Channels in the second superfamily include the inward rectifiers (KIR) and the ATP-sensitive K-channel (KATP). Their tetrameric assembly of alpha-subunits contains only two transmembrane-spanning segments and lacks a voltage sensor. KATP is associated with a sulphonylurea binding site belonging to the ATP-binding cassette family. Although KIR conducts poorly at potentials positive to EK, both it and KATP do conduct over the physiological potential range. K-channel modulators are important in determining channel function. These include drugs like tetraethylammonium and 4-aminopyridine and more recently-discovered selective agents active at KATP and BKCa. These are typified by diazoxide, levcromakalim and glibenclamide and by NS1619, iberiotoxin and penitrem A, respectively.