5-HT2 receptors-mediated modulation of voltage-gated K+ channels and neurophysiopathological correlates

D’Adamo, Maria Cristina; Servettini, Ilenio; Guglielmi, Luca; Matteo, Vincenzo Di; Maio, Roberto Di; Giovanni, Giuseppe Di; Pessia, Mauro

doi:10.1007/s00221-013-3555-8

Cited by 12 publications

(9 citation statements)

References 62 publications

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“…Kv channels regulate the duration of action potentials, modulate the release of neurotransmitters, control the excitability, electrical properties, and firing pattern of central and peripheral neurons (Pessia, 2004). Moreover, the activity of Kv channels can be dynamically modulated by several events, including neurotransmitter- stimulated biochemical cascades (Imbrici et al, 2000; D'Adamo et al, 2013). Knowledge of their precise targeting and neurophysiological functions has important implications for defining the roles played by each Kv channel type in the pathophysiology of epilepsy.…”

Section: Voltage-gated K+ Channels and Channelepsymentioning

confidence: 99%

“…Neurons store and convey information in the form of electrical impulses generated by ion channels. Neuronal excitability can be controlled by both the intrinsic activity of K + channels and the receptors-mediated modulation of their activity (Pessia et al, 1994; Imbrici et al, 2000; Pessia, 2004; D'Adamo et al, 2013). Their opening and resulting outward K + flux dampen neuronal excitability and therefore they are viewed as inhibitory channels.…”

Section: Introductionmentioning

confidence: 99%

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K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

D’Adamo

Catacuzzeno

Giovanni

et al. 2013

Front. Cell. Neurosci.

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105

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K+ channels are important determinants of seizure susceptibility. These membrane proteins, encoded by more than 70 genes, make the largest group of ion channels that fine-tune the electrical activity of neuronal and non-neuronal cells in the brain. Their ubiquity and extremely high genetic and functional diversity, unmatched by any other ion channel type, place K+ channels as primary targets of genetic variations or perturbations in K+-dependent homeostasis, even in the absence of a primary channel defect. It is therefore not surprising that numerous inherited or acquired K+ channels dysfunctions have been associated with several neurologic syndromes, including epilepsy, which often generate confusion in the classification of the associated diseases. Therefore, we propose to name the K+ channels defects underlying distinct epilepsies as “K+ channelepsies,” and introduce a new nomenclature (e.g., Kx.y-channelepsy), following the widely used K+ channel classification, which could be also adopted to easily identify other channelopathies involving Na+ (e.g., Navx.y-phenotype), Ca2+ (e.g., Cavx.y-phenotype), and Cl− channels. Furthermore, we discuss novel genetic defects in K+ channels and associated proteins that underlie distinct epileptic phenotypes in humans, and analyze critically the recent progress in the neurobiology of this disease that has also been provided by investigations on valuable animal models of epilepsy. The abundant and varied lines of evidence discussed here strongly foster assessments for variations in genes encoding for K+ channels and associated proteins in patients with idiopathic epilepsy, provide new avenues for future investigations, and highlight these proteins as critical pharmacological targets.

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Section: Voltage-gated K+ Channels and Channelepsymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

D’Adamo

Catacuzzeno

Giovanni

et al. 2013

Front. Cell. Neurosci.

Self Cite

105

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“…The response of 5-HT 2A Rs is mediated by a decrease in Kv conductance 9 , 16 – 18 . Noticeably, hallucinogens other than PCP derivatives (such as LSD) have also been reported to modulate Kv channel activity, acting at 5-HT2Rs 9 . In particular, Kv1.5 has been reported to be primarily responsible for mediating 5-HT 2A R activation in the arteries 18 .…”

Section: Resultsmentioning

confidence: 99%

Enhancement of 5-HT2A receptor function and blockade of Kv1.5 by MK801 and ketamine: implications for PCP derivative-induced disease models

et al. 2018

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MK801 and ketamine, which are phencyclidine (PCP) derivative N-methyl-d-aspartate receptor (NMDAr) blockers, reportedly enhance the function of 5-hydroxytryptamine (HT)-2A receptors (5-HT2ARs). Both are believed to directly affect the pathogenesis of schizophrenia, as well as hypertension. 5-HT2AR signaling involves the inhibition of Kv conductance. This study investigated the interaction of these drugs with Kv1.5, which plays important roles in 5-HT2AR signaling and in regulating the excitability of the cardiovascular and nervous system, and the potential role of this interaction in the enhancement of the 5-HT2AR-mediated response. Using isometric organ bath experiments with arterial rings and conventional whole-cell patch-clamp recording of Chinese hamster ovary (CHO) cells ectopically overexpressing Kv1.5, we examined the effect of ketamine and MK801 on 5-HT2AR-mediated vasocontraction and Kv1.5 channels. Both ketamine and MK801 potentiated 5-HT2AR-mediated vasocontraction. This potentiation of 5-HT2AR function occurred in a membrane potential-dependent manner, indicating the involvement of ion channel(s). Both ketamine and MK801 rapidly and directly inhibited Kv1.5 channels from the extracellular side independently of NMDArs. The potencies of MK801 in facilitating the 5-HT2AR-mediated response and blocking Kv1.5 were higher than those of ketamine. Our data demonstrated the direct inhibition of Kv1.5 channels by MK801/ketamine and indicated that this inhibition may potentiate the functions of 5-HT2ARs. We suggest that 5-HT2AR-Kv1.5 may serve as a receptor-effector module in response to 5-HT and is a promising target in the pathogenesis of MK801-/ketamine-induced disease states such as hypertension and schizophrenia.

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“…These channels occur both in the CNS and peripheral organs, including the heart, kidney and lungs; they play major roles in normal physiologic processes and contribute to pathologies as diverse as cancer and diabetes (see 88,95,317,319,481,528,548,554 for reviews of K + channels in the brain). Under most conditions, opening of these channels results in an increased flow of K + ions out of the cell and, consequently, a shift toward a more hyperpolarized membrane potential.…”

Section: Neurotransmitters and Peptides Exerting State-dependent Contmentioning

confidence: 99%

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

Kubin

2016

Comprehensive Physiology

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Upper airway muscles subserve many essential for survival orofacial behaviors, including their important role as accessory respiratory muscles. In the face of certain predisposition of craniofacial anatomy, both tonic and phasic inspiratory activation of upper airway muscles is necessary to protect the upper airway against collapse. This protective action is adequate during wakefulness, but fails during sleep which results in recurrent episodes of hypopneas and apneas, a condition known as the obstructive sleep apnea syndrome (OSA). Although OSA is almost exclusively a human disorder, animal models help unveil the basic principles governing the impact of sleep on breathing and upper airway muscle activity. This article discusses the neuroanatomy, neurochemistry, and neurophysiology of the different neuronal systems whose activity changes with sleep-wake states, such as the noradrenergic, serotonergic, cholinergic, orexinergic, histaminergic, GABAergic and glycinergic, and their impact on central respiratory neurons and upper airway motoneurons. Observations of the interactions between sleep-wake states and upper airway muscles in healthy humans and OSA patients are related to findings from animal models with normal upper airway, and various animal models of OSA, including the chronic-intermittent hypoxia model. Using a framework of upper airway motoneurons being under concurrent influence of central respiratory, reflex and state-dependent inputs, different neurotransmitters, and neuropeptides are considered as either causing a sleep-dependent withdrawal of excitation from motoneurons or mediating an active, sleep-related inhibition of motoneurons. Information about the neurochemistry of state-dependent control of upper airway muscles accumulated to date reveals fundamental principles and may help understand and treat OSA.

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5-HT2 receptors-mediated modulation of voltage-gated K+ channels and neurophysiopathological correlates

Cited by 12 publications

References 62 publications

K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy

Enhancement of 5-HT2A receptor function and blockade of Kv1.5 by MK801 and ketamine: implications for PCP derivative-induced disease models

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

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