KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents

KCNQ2 and KCNQ3, both of which are mutated in a type of human neonatal epil epsy, form heteromeric potassium channels that are expressed in broad regio ns of the brain. The associated current may be identical to the M-current, an important regulator of neuronal excitability. We now show that the RNA e ncoding the novel KCNQ5 channel is: also expressed in brain and in sympathe tic ganglia where it overlaps largely with KCNQ2 and KCNQ3. In addition, it is expressed in skeletal muscle, KCNQ5 yields currents that activate slowl y with depolarization and can form heteromeric channels with KCNQ3, Current s expressed from KCNQ5 have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic recept or activation. A KCNQ5 splice variant found in skeletal muscle displays alt ered gating kinetics. This indicates a molecular diversity of channels yiel ding M-type currents and suggests a role for KCNQ5 in the regulation of neu ronal excitability.