Kv7 channels: interaction with dopaminergic and serotonergic neurotransmission in the CNS.
Neuronal Kv7 channels (also termed KCNQ channels) are the molecular correlate of the M-current. The Kv7 channels activate at rather negative membrane potentials (< or = 60 mV), thereby 'fine-tuning' the resting membrane potential. The Kv7 channels are widely expressed in the brain with the Kv7.2, Kv7.3 and Kv7.5 channels being the most abundant. The Kv7.4 subunit has the most restricted brain regional expression being present in discrete nuclei of brainstem only. Kv7 channels are expressed at different subcellular locations, being on both somatodendritic, axonal and terminal sites. This complex subcellular distribution of Kv7 channels enables them to participate in both pre- and postsynaptic modulation of basal and stimulated excitatory neurotransmission. Activation of neuronal Kv7 channels limits repetitive firing thereby potentially limiting the generation of long bursts, with subsequent inhibition of monoaminergic neurotransmitter release. In this review, we focus on the influence of Kv7 channels on dopaminergic and serotonergic neurotransmission. The data suggest a novel action of Kv7 channel openers which could translate into having therapeutic value in the treatment of disease states characterized by overactivity of dopaminergic (e.g. schizophrenia and drug abuse) and serotonergic neurotransmission (e.g. anxiety).
Hansen
Henrik H
HH
Department of Translational Neurobiology, NeuroSearch A/S, Pederstrupvej 93, DK-2750 Ballerup, Denmark. heh@neurosearch.dk
Waroux
Olivier
O
Seutin
Vincent
V
Jentsch
Thomas J
TJ
Aznar
Susana
S
Mikkelsen
Jens D
JD
D002490:Central Nervous System / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D006801:Humans; D051656:KCNQ Potassium Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D051656:KCNQ Potassium Channels; D012701:Serotonin; D004298:Dopamine