Kv7 potassium channel subunits and M currents in cultured hippocampal interneurons

Grigorov, A. O.; Moskalyuk, A. A.; Kravchenko, Mykola; Veselovsky, N. S.; Verkhratsky, Alexei; Fedulova, S. A.

doi:10.1007/s00424-013-1406-x

Cited by 15 publications

(9 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, conditional homozygote deletion of Kcnq2 in PNs is sufficient to cause epilepsy in Emx1 Cre ; Kcnq2 fl/fl mice (Soh et al, 2014). However, Kcnq2 is also expressed in GABAergic INs, as was shown in different sub-population of hippocampal INs (both regular and PV-positive FS INs) (Grigorov et al, 2014, Cooper et al, 2001). In the hippocampus, Kv7 channels regulate interspike intervals of O-LM SSTpositive INs (Lawrence et al, 2006).…”

Section: Voltage-gated Potassium Channelsmentioning

confidence: 85%

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

Jiang

Lachance

Rossignol

2016

Progress in Brain Research

View full text Add to dashboard Cite

GABAergic interneurons of the parvalbumin-positive fast-spiking basket cells subtype (PV INs) are important regulators of cortical network excitability and of gamma oscillations, involved in signal processing and cognition. Impaired development or function of PV INs has been associated with epilepsy in various animal models of epilepsy, as well as in some genetic forms of epilepsy in humans. In this review, we provide an overview of some of the experimental data linking PV INs dysfunction with epilepsy, focusing on disorders of the specification, migration, maturation, synaptic function, or connectivity of PV INs. Furthermore, we reflect on the potential therapeutic use of cell-type specific stimulation of PV INs within active networks and on the transplantation of PV INs precursors in the treatment of epilepsy and its comorbidities.

show abstract

Section: Voltage-gated Potassium Channelsmentioning

confidence: 85%

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

Jiang

Lachance

Rossignol

2016

Progress in Brain Research

View full text Add to dashboard Cite

show abstract

“…Studies have essentially been performed in hippocampal interneurons where expression and modulation of neuronal firing by Kv7 channels have been demonstrated for regular and fast spiking interneurons maintained in primary hippocampal cultures (Grigorov et al, 2014), in a subset of somatostatin oriens-lacunosum moleculare (OLM) interneurons and paravalbumin expressing interneurons in the CA1 region of the hippocampus; in the basket cells, OLM and bistratified interneurons of the CA3 region of the hippocampus (Lawrence et al, 2006;Nieto-Gonzalez and Jensen 2013;Fidzinski et al, 2015;Soh et al2018). Recent data provided also evidences for the modulation of neuronal firing by Kv7 channels of paravalbumin expressing interneurons in the layer II/III of the somatosensory cortex (Soh et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Time-limited alterations in cortical activity of a Knock-in mice model ofKCNQ2-related Developmental and Epileptic Encephalopathy

Biba

Kurz

Villard

et al. 2020

Preprint

View full text Add to dashboard Cite

De novo variants in the KCNQ2 gene encoding the Kv7.2 subunit of the voltage-gated potassium Kv7/M channel are the main cause of Early Onset Epileptic Encephalopathy (EOEE) with suppression burst suggesting that this channel plays an important role for proper brain development. Functional analysis of these variants in heterologous cells has shown that most of them are loss of function leading to a reduction of M current. However the cellular mechanism of the neuronal network dysfunctionning is still not known. Here we characterized the electrophysiological properties of developing pyramidal cells of the layer II/III and V and analyzed spontaneous synaptic activity in these layers in motor cortical slices obtained from a recently generated heterozygous knock-in mouse harboring the loss-of-function pathogenic p.T274M variant. Experiments were performed on animals aged one week, three weeks and four-five weeks, and the results were compared with those of pyramidal cells recorded in slices from wild-type mice untreated or treated with the Kv7 channel blocker XE-991. We showed that the variant led to a hyperexcitability of pyramidal cells of layer II/III in cortical slices from animal aged 1 week and 3 weeks and to a level that was similar to the effect of XE-911. In layer V the impact of the variant was observed in slices from animal aged 3 weeks but not earlier and to a level that was lower to the effect of XE-991. However, in cortical slices from animal aged 4-5 weeks electrophysiological properties of pyramidal cells of layers II/III and V were no more affected by the variant but still sensitive to XE-991. The recovery of the electrophysiological responses in knock-in animals was associated with a slight but significant distal shift of the axonal initial segment (AIS) from the soma of pyramidal cells of layer II/III and V. Recordings of spontaneous synaptic activity in these layers revealed the presence of recurrent GABAergic network activities (RGNA) that were mainly observed during the three first postnatal weeks of life and which occurrence and frequency were increased in pyramidal cells of the layer II/III but not of the layer V of the knock-in mouse. There were no significant differences in synaptic activities mediated by GABA and glutamate receptors in cortical slices from animal aged 4-5 weeks. Together our data provided evidences that the heterozygous p.T274M variant impacts the activity of pyramidal cells and probably of Gabaergic interneurons during a limited period of development. Our data also indicated that neurons of the layer II/III are more sensitive to the variant than those located in the layer V in terms of age of onset, neuronal firing and spontaneous synaptic activities. Moreover our data suggest that a compensatory mechanism might take place in the knock-in mice aged 4-5 weeks allowing the recovery of control activity at cellular and network levels and which is associated with a slight displacement of the AIS. Thus, the effect of the variant on neuronal activity is developmentally regulated a...

show abstract

“…The mechanism of disease for gain-offunction mutations is less clear. Both K V 7.2 and K V 7.3 proteins are found in parvalbumin-positive hippocampal interneurons (Lawrence et al, 2006;Nieto-Gonzalez and Jensen, 2013;Grigorov et al, 2014) with a reduction in spike adaption in these cells possibly increasing network excitability. The K V 7.2 (A306T) and K V 7.3 (G311V) knock-in mouse models are both based on loss-of-function mutations found in benign familial neonatal convulsions (Singh et al, 2008;Otto et al, 2009).…”

Section: Ion Channels In Genetic Epilepsymentioning

confidence: 99%

Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies

Oyrer¹,

Maljevic²,

Scheffer³

et al. 2017

Pharmacol Rev

225

190

View full text Add to dashboard Cite

Epilepsy is a common and serious neurologic disease with a strong genetic component. Genetic studies have identified an increasing collection of disease-causing genes. The impact of these genetic discoveries is wide reaching-from precise diagnosis and classification of syndromes to the discovery and validation of new drug targets and the development of disease-targeted therapeutic strategies. About 25% of genes identified in epilepsy encode ion channels. Much of our understanding of disease mechanisms comes from work focused on this class of protein. In this study, we review the genetic, molecular, and physiologic evidence supporting the pathogenic role of a number of different voltage- and ligand-activated ion channels in genetic epilepsy. We also review proposed disease mechanisms for each ion channel and highlight targeted therapeutic strategies.

show abstract

Kv7 potassium channel subunits and M currents in cultured hippocampal interneurons

Cited by 15 publications

References 33 publications

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy

Time-limited alterations in cortical activity of a Knock-in mice model ofKCNQ2-related Developmental and Epileptic Encephalopathy

Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies

Contact Info

Product

Resources

About