THE ROLE OF POTASSIUM CHANNELS IN EXCITABLE CELLS

Potassium (K) channels regulate cellular excitability. Their opening h yperpolarises the membrane potential and induces quiescence whereas th eir closure produces depolarisation and excitation. One K-channel supe rfamily includes the delayed rectifier (K-V), the A-type (K-A) and the large conductance, Ca-sensitive (BKCa) channels. These serve to termi nate excitatory events and consist of a tetramer of alpha-subunits eac h comprising six transmembrane-spanning segments including a voltage-s ensor. Additional beta-subunits which modify inactivation and voltage sensitivity may also be present. Channels in the second superfamily in clude the inward rectifiers (K-IR) and the ATP-sensitive K-channel (K- ATP). Their tetrameric assembly of alpha-subunits contains only two tr ansmembrane-spanning segments and lacks a voltage sensor. K-IR is asso ciated with a sulphonylurea binding site belonging to the ATP-binding cassette family. Although K-IR conducts poorly at potentials positive to E(K), both it and K-ATP do conduct over the physiological potential range. K-channel modulators are important in determining channel func tion. These include drugs like tetraethylammonium and 4-aminopyridine and more recently-discovered selective agents active at K-ATP and BKCa . These are typified by diazoxide, levcromakalim and glibenclamide and by NS1619, iberiotoxin and penitrem A, respectively.