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Review
. 2008 Apr 1;586(7):1823-32.
doi: 10.1113/jphysiol.2007.149450. Epub 2008 Jan 3.

Kv7 channels: interaction with dopaminergic and serotonergic neurotransmission in the CNS

Henrik H Hansen  1 , Olivier Waroux, Vincent Seutin, Thomas J Jentsch, Susana Aznar, Jens D Mikkelsen
Affiliations
Review

Kv7 channels: interaction with dopaminergic and serotonergic neurotransmission in the CNS

Henrik H Hansen et al. J Physiol. .

Abstract

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).

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Figures

Figure 1
Figure 1. Schematized drawing of the subcellular topography of Kv7 channel expression in a principal mesencephalic dopaminergic neuron
Kv7.2-Kv7.5 channels are indicated at different principal subcellular positions where Kv7 channel mRNA and/or protein expression has been reported. Note that the Kv7.4 channels are expressed only in mesencephalic dopaminergic neurons at somatodendritic sites, whereas Kv7.2 and Kv7.3 channels are found at several cellular pre- and postsynaptic locations. Modified from Kandal ER, Jessell TM & Schwartz JH (2000), Principles of Neural Science, McGraw-Hill Medical, reproduced with permission of the McGraw-Hill Companies.
Figure 2
Figure 2. Immunohistochemical staining of Kv7.4 channels in the rat substantia nigra pars compacta (SNc, A–C) and ventral tegmental area (VTA, A)
Note that the substantia nigra pars reticulata (SNr) is practically devoid of Kv7.4 immunoreactivity (A and B, 5x and 20× magnification, respectively). C, Kv7.4 positive neurons in the SNc, showing the presence of somatodendritic Kv7.4 channel protein expression (40× magnification). The Kv7.4 subunit is localized to the plasma membrane and dendrites as well as in intracellular membranes, being in agreement with Kharkovets et al. (2000). A rabbit polyclonal Kv7.4 channel antibody was used (Kharkovets et al. 2000) and immunoreactivity was detected by means of the avidin–biotin method using diaminobenzidine as chromagen and the reaction was amplified using the biotinylated tyramine procedure as previously described (Hansen et al. 2006).
Figure 3
Figure 3. Kv7.4 channel expression in the raphe nuclei
A, representative immunohistochemical staining of Kv7.4 channels in the rat dorsal (DRN) and median raphe (MNR) nucleus of the rat brainstem (10× magnification, 40 μm section). B, further caudal level of the DRN (20× magnification, 40 μm section). The data indicate that Kv7.4 channels are expressed throughout the DRN at the rostral–caudal level. A rabbit polyclonal Kv7.4 channel antibody (Kharkovets et al. 2000) diluted 1: 5000 and biotinylated donkey anti-rabbit IgG (1: 800; Jackson ImmunoResearch Laboratories, West grove, PA, USA) were used. Immunoreactivity was detected by means of the avidin–biotin amplification method using diaminobenzidine as chromagen and amplified using the biotinylated tyramine procedure as previously described (Hansen et al. 2006).
Figure 4
Figure 4. Kv7.4 channels are expressed in serotonergic (5-HT) neurons in the rat DRN
Upper panels (40× magnification, 40 μm section): Confocal scanning of Kv7.4 and 5-HT immunoreactivity shows an overlap of Kv7.4 channel and 5-HT expression in a subpopulation of neurons in the rat dorsal raphe nucleus (DRN). Lower panels (40× magnification, 40 μm section): Representative retrograde tracing experiment showing that Kv7.4 channels colocalize with rhodamine-coupled latex microsphere retrobeads (Lumaflour, Naples, FL, USA) pressure-injected unilaterally into the rat hippocampus, indicating that Kv7.4 channels are expressed in several DRN neurons projecting to the hippocampus. After 10 days the rat was perfused and 40 μm DRN sections processed for double immunohistochemistry. A rabbit polyclonal Kv7.4 channel (Kharkovets et al. 2000) diluted 1: 5000 and mouse monoclonal 5-HT antibody (1: 5000; DiaSorin, Saluggia, Italy) were used. The secondary antibodies were either Cy3-conjugated sheep anti-mouse IgG (1: 200) or Alexa 633-conjugated donkey anti-mouse/goat IgG (1: 200) mixed with biotinylated donkey anti-rabbit IgG (1: 800) (all from Jackson ImmunoResearch Laboratories, West grove, PA, USA). The immunoreactions were completed using the biotinylated tyramine procedure as previously described together with Fluorescein Avidin D (1: 200; Vector Laboratories, Burlingame, CA, USA) as previously described (Hansen et al. 2006).
Figure 5
Figure 5. Extracellular recording of a neuron in the anterior part of the rat DRN in vitro
The method has been previously described (Seutin et al. 1990). Retigabine induces a concentration-dependent inhibition of the firing rate of the cell. Unlike the situation in vivo in which the majority of DRN serotonergic neurons are spontaneously active, most DRN serotonergic neurons are silent in a slice preparation. In the presence of 10 μm phenylephrine, they fire at a rate of 0.5–5 spikes per second and are characterized by long duration (2 ms), often triphasic action potentials. Neuronal spike activity is completely inhibited by nanomolar concentrations of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT), which strongly suggests that the neuron is serotonergic.
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References

    1. Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci. 2005;8:365–371. - PubMed
    1. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK. A potassium channel mutation in neonatal human epilepsy. Science. 1998;279:403–406. - PubMed
    1. Blackburn-Munro G, Dalby-Brown W, Mirza NR, Mikkelsen JD, Blackburn-Munro RE. Retigabine: chemical synthesis to clinical application. CNS Drug Rev. 2005;11:1–20. - PMC - PubMed
    1. Bonjean M, Waroux O, Dang-Vu T, Phillips C, Lamy C, Scuvee-Moreau J, Sepulchre R, Maquet P, Seutin V. 2007 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience; 2007. Effect of the M-current on the excitability of midbrain dopaminergic neurons: a computational study. Program No. 681.6.
    1. Cooper EC, Harrington E, Jan YN, Jan LY. M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain. J Neurosci. 2001;21:9529–9540. - PMC - PubMed

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