Pathways modulating neural KCNQ/M (Kv7) potassium channels

Delmas, Patrick; Brown, D. A.

doi:10.1038/nrn1785

Cited by 627 publications

(702 citation statements)

References 122 publications

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“…Depending on the actual subtype, muscarinic receptor activation may cause Ca 2+ release from intracellular stores and/or may evoke depolarisation (e.g., by closing the KCNQ/M-type K + channels), which in turn induces action potential firing and consequent Ca 2+ entry from the extracellular space [7]. Although there were no specific efforts in the present work to identify the exact mechanism underlying the generation of the Ca 2+ transients recorded from the granule cells, their action potential-coupled character, the contribution of the Ca 2+ entry, and the decisive involvement of the M3 receptors in the genesis of the rapid Ca 2+ transients were clearly established.…”

Section: Muscarinic Modulation Of Dcn Granule Cellsmentioning

confidence: 99%

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

Kőszeghy

Vincze

Rusznák

et al. 2012

Pflugers Arch - Eur J Physiol

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Acetylcholine modulates the function of the cochlear nucleus via several pathways. In this study the effects of cholinergic stimulation were studied on the cytoplasmic Ca 2+ concentration of granule neurones of the rat dorsal cochlear nucleus (DCN). Ca 2+ transients were recorded in Oregon-Green-BAPTA 1-loaded brain slices using a calcium imaging technique. For the detection, identification, and characterisation of the Ca 2+ transients, a wavelet analysis-based method was developed. Granule cells were identified on the basis of their size and localisation. The action potential-coupled character of the Ca 2+ transients of the granule cells was established by recording fluorescence changes and electrical activity simultaneously. Application of the cholinergic agonist carbamyl-choline (CCh) significantly increased the frequency of the Ca 2+ transients (from 0.37 to 6.31 min -1 , corresponding to a 17.1-fold increase; n = 89).This effect was antagonised by atropine, whereas CCh could still evoke an 8.3-fold increase of the frequency of the Ca 2+ transients when hexamethonium was present.Using immunolabelling, the expression of both type 1 and type 3 muscarinic receptors (M1 and M3 receptors, respectively) was demonstrated in the granule cells. Application of 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (an M3-specific antagonist) prevented the onset of the CCh effect, whereas an M1-specific antagonist (pirenzepine) was less effective. We conclude that cholinergic stimulation increases the activity of granule cells, mainly by acting on their M3 receptors. The modulation of the firing activity of the granule cells, in turn, may modify the firing of projection neurones, and may adjust signal processing in the entire DCN.

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Section: Muscarinic Modulation Of Dcn Granule Cellsmentioning

confidence: 99%

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

Kőszeghy

Vincze

Rusznák

et al. 2012

Pflugers Arch - Eur J Physiol

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“…First, Li þ inhibits several cellular enzymes involved in inositol recycling, a crucial step in the synthesis of the PIP2, 43 a membrane phospholipid that is essential for KCNQ2 activity and for its regulation by acetylcholine as well as by other neurotransmitters and peptides. [44][45][46] Li þ by interfering with this pathway of regulation will necessarily interfere with KCNQ2 activity either basic or regulated by neurotransmitters such as acetylcholine acting on the M1 receptor. Second, the kinase GSK3b has also been shown to be inhibited by Li þ 43,47 and we have shown in this paper that GSK3b can, in vitro, phosphorylate KCNQ2 and that this phosphorylation is decreased by Li þ .…”

Section: Pp2a-bc and Kcnq2 In Bipolar Diseasementioning

confidence: 99%

PP2A-Bγ subunit and KCNQ2 K+ channels in bipolar disorder

Borsotto

Cavarec²,

Bouillot³

et al. 2006

Pharmacogenomics J

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Many bipolar affective disorder (BD) susceptibility loci have been identified but the molecular mechanisms responsible for the disease remain to be elucidated. In the locus 4p16, several candidate genes were identified but none of them was definitively shown to be associated with BD. In this region, the PPP2R2C gene encodes the Bg-regulatory subunit of the protein phosphatase 2A (PP2A-Bg). First, we identified, in two different populations, single nucleotide polymorphisms and risk haplotypes for this gene that are associated to BD. Then, we used the Bg subunit as bait to screen a human brain cDNA library with the yeast two-hybrid technique. This led us to two new splice variants of KCNQ2 channels and to the KCNQ2 channel itself. This unusual K þ channel has particularly interesting functional properties and belongs to a channel family that is already known to be implicated in several other monogenic diseases. In one of the BD populations, we also found a genetic association between the KCNQ2 gene and BD. We show that KCNQ2 splice variants differ from native channels by their shortened C-terminal sequences and are unique as they are active and exert a dominant-negative effect on KCNQ2 wild-type (wt) channel activity. We also show that the PP2A-Bg subunit significantly increases the current generated by KCNQ2wt, a channel normally inhibited by phosphorylation. The kinase glycogen synthase kinase 3 beta (GSK3b) is considered as an interesting target of lithium, the classical drug used in BD. GSK3b phosphorylates the KCNQ2 channel and this phosphorylation is decreased by Li þ .

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“…Activation of G q/11 -coupled receptors induces activation of non-selective cation (NSC) channels and inhibition of K + channels (Delmas et al, 2004;Delmas and Brown, 2005;Moran et al, 2004), both of which contribute to depolarization, in various types of neurons including hippocampal neurons (Chiang et al, 2010;Congar et al, 1997;Gee et al, 2003). In the present study, we used these channel modulations as examples of cellular responses elicited by receptor-driven PLCβ activation, and examined whether they are Ca 2+ dependent.…”

Section: Introductionmentioning

confidence: 99%