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 epilepsy, form heteromeric potassium channels that are expressed in broad regions 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 encoding the novel KCNQ5 channel is also expressed in brain and in sympathetic ganglia where it overlaps largely with KCNQ2 and KCNQ3. In addition, it is expressed in skeletal muscle. KCNQ5 yields currents that activate slowly with depolarization and can form heteromeric channels with KCNQ3. Currents expressed from KCNQ5 have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. A KCNQ5 splice variant found in skeletal muscle displays altered gating kinetics. This indicates a molecular diversity of channels yielding M-type currents and suggests a role for KCNQ5 in the regulation of neuronal excitability.
Schroeder
B C
BC
Zentrum für Molekulare Neurobiologie Hamburg, Hamburg University, Martinistrasse 85, D-20246 Hamburg, Germany.
Hechenberger
M
M
Weinreich
F
F
Kubisch
C
C
Jentsch
T J
TJ
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D004553:Electric Conductivity; D004594:Electrophysiology; D006801:Humans; D017403:In Situ Hybridization; D051656:KCNQ Potassium Channels; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D017386:Sequence Homology, Amino Acid; D017783:Superior Cervical Ganglion / Q000737:chemistry; D014018:Tissue Distribution
D051656:KCNQ Potassium Channels; C412231:KCNQ5 protein, human; C501028:Kcnq5 protein, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger