Pharmacological modulation of the voltage-gated neuronal Kv7/KCNQ/M-channel alters the intrinsic excitability and synaptic responses of pyramidal neurons in rat prefrontal cortex slices

Peng, Hui; Bian, Xue-Bin; Ma, Fu-Cui; Wang, Kewei

doi:10.1038/aps.2017.72

Cited by 36 publications

(26 citation statements)

References 44 publications

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“…Therefore, they can play an important role in modulating subthreshold membrane properties. KCNQ inhibition can also make neurons more responsive to synaptic inputs (i.e., larger EPSPs with the same presynaptic condition) [71]. The type I hair cellcalyx synapse is unique in that in addition to the typical quantal signal transmission, it also provides a non-quantal component that is mediated by accumulation of K + , glutamate, and H + in the closed synaptic space between the calyx and type I hair cell [52,62,64,[72][73][74][75].…”

Section: Modulation Of Subthreshold Potentials By Efferents: Effects mentioning

confidence: 99%

Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery

et al. 2021

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Vestibular nerve afferents are divided into regular and irregular groups based on the variability of interspike intervals in their resting discharge. Most afferents receive inputs from bouton terminals that contact type II hair cells as well as from calyx terminals that cover the basolateral walls of type I hair cells. Calyces have an abundance of different subtypes of KCNQ (Kv7) potassium channels and muscarinic acetylcholine receptors (mAChRs) and receive cholinergic efferent inputs from neurons in the brainstem. We investigated whether mAChRs affected membrane properties and firing patterns of calyx terminals through modulation of KCNQ channel activity. Patch clamp recordings were performed from calyx terminals in central regions of the cristae of the horizontal and anterior canals in 13 -18 day old Sprague-Dawley rats. KCNQ mediated currents were observed as voltage sensitive currents with slow kinetics (activation and deactivation), resulting in spike frequency adaptation so that calyces at best fired a single action potential at the beginning of a depolarizing step. Activation of mAChRs by application of oxotremorine methiodide or inhibition of KCNQ channels by linopirdine dihydrochloride decreased voltage activated currents by ~30%, decreased first spike latencies by ~40%, decreased spike thresholds by ~50%, and resulted in continuous firing during depolarizing steps. Interestingly, some of the calyces showed spontaneous discharge in the presence of these drugs. Together, these findings suggest that cholinergic efferents can modulate the response properties and encoding of head movements by afferents.

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Section: Modulation Of Subthreshold Potentials By Efferents: Effects mentioning

confidence: 99%

Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery

et al. 2021

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“…Elevated activity in the amygdala is associated with increased anxiety and perception of fear, whereas the medial prefrontal cortex (PFC) exerts an inhibitory effect on the amygdala . Considering the enrichment of K v 7.2 in the medial PFC but not the amygdala, reduced anxiety and/or perception of danger and fear could be attributed to inhibition of amygdala by increased medial PFC activity in KCNQ2 +/− mice.…”

Section: Discussionmentioning

confidence: 99%

“…118,119 Socially, dominant mice display increased excitatory synaptic strength in layer V pyramidal neurons in the medial PFC 69 where K v 7.2 is highly expressed 16,17 (alleninstitute.org/). Because K v 7 current suppresses intrinsic excitability and postsynaptic transmission of PFC layer V pyramidal neurons, 94 the heterozygous loss of K v 7.2 may likely contribute to the increased social dominant behaviors in KCNQ2 +/− mice by increasing the activity of PFC layer V pyramidal neurons.…”

Section: Role Of K V 7 Channels In Social Dominance and Aggressionmentioning

confidence: 99%

Heterozygous loss of epilepsy geneKCNQ2alters social, repetitive and exploratory behaviors

Kim

Patel

Zhang

et al. 2019

Genes Brain and Behavior

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KCNQ/K v 7 channels conduct voltage-dependent outward potassium currents that potently decrease neuronal excitability. Heterozygous inherited mutations in their principle subunits K v 7.2/KCNQ2 and K v 7.3/KCNQ3 cause benign familial neonatal epilepsy whereas patients with de novo heterozygous K v 7.2 mutations are associated with early-onset epileptic encephalopathy and neurodevelopmental disorders characterized by intellectual disability, developmental delay and autism. However, the role of K v 7.2-containing K v 7 channels in behaviors especially autism-associated behaviors has not been described. Because pathogenic K v 7.2 mutations in patients are typically heterozygous loss-of-function mutations, we investigated the contributions of K v 7.2 to exploratory, social, repetitive and compulsive-like behaviors by behavioral phenotyping of both male and female KCNQ2 +/− mice that were heterozygous null for the KCNQ2 gene. Compared with their wild-type littermates, male and female KCNQ2 +/− mice displayed increased locomotor activity in their home cage during the light phase but not the dark phase and showed no difference in motor coordination, suggesting hyperactivity during the inactive light phase. In the dark phase, KCNQ2 +/− group showed enhanced exploratory behaviors, and repetitive grooming but decreased sociability with sex differences in the degree of these behaviors. While male KCNQ2 +/− mice displayed enhanced compulsive-like behavior and social dominance, female KCNQ2 +/− mice did not. In addition to elevated seizure susceptibility, our findings together indicate that heterozygous loss of K v 7.2 induces behavioral abnormalities including autism-associated behaviors such as reduced sociability and enhanced repetitive behaviors. Therefore, our study is the first to provide a tangible link between loss-of-function K v 7.2 mutations and the behavioral comorbidities of K v 7.2-associated epilepsy.

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“…KCNQ channels are of great interest, as they have powerful influences on firing patterns (Greene and Hoshi, 2017; Gu et al, 2005; Guan et al, 2011; Peng et al, 2017; Santini and Porter, 2010; Yue and Yaari, 2004), and because their open state is regulated by many neuromodulators and second messenger actions, and thus can serve as the intermediary for altering neuronal excitability based on arousal state (Delmas and Brown, 2005; Greene and Hoshi, 2017). KCNQ channels are also called Kv7 channels or “M” channels (mediating the M-current, I M ), as they are closed by muscarinic receptor stimulation (Brown and Adams, 1980; Delmas and Brown, 2005).…”

Section: Introductionmentioning

confidence: 99%

Role of KCNQ potassium channels in stress-induced deficit of working memory

Arnsten

Jin

Gamo

et al. 2019

Neurobiology of Stress

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The prefrontal cortex (PFC) mediates higher cognition but is impaired by stress exposure when high levels of catecholamines activate calcium-cAMP-protein kinase A (PKA) signaling. The current study examined whether stress and increased cAMP-PKA signaling in rat medial PFC (mPFC) reduce pyramidal cell firing and impair working memory by activating KCNQ potassium channels. KCNQ2 channels were found in mPFC layers II/III and V pyramidal cells, and patch-clamp recordings demonstrated KCNQ currents that were increased by forskolin or by chronic stress exposure, and which were associated with reduced neuronal firing. Low dose of KCNQ blockers infused into rat mPFC improved cognitive performance and prevented acute pharmacological stress-induced deficits. Systemic administration of low doses of KCNQ blocker also improved performance in young and aged rats, but higher doses impaired performance and occasionally induced seizures. Taken together, these data demonstrate that KCNQ channels have powerful influences on mPFC neuronal firing and cognitive function, contributing to stress-induced PFC dysfunction.

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Pharmacological modulation of the voltage-gated neuronal Kv7/KCNQ/M-channel alters the intrinsic excitability and synaptic responses of pyramidal neurons in rat prefrontal cortex slices

Cited by 36 publications

References 44 publications

Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery

Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery

Heterozygous loss of epilepsy geneKCNQ2alters social, repetitive and exploratory behaviors

Role of KCNQ potassium channels in stress-induced deficit of working memory

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