Regulation of Neuronal Ion Channels by G‐Protein‐Coupled Receptors in Sympathetic Neurons

Shapiro, Mark S.; Gamper, Nikita

doi:10.1002/9780470429907.ch11

Cited by 4 publications

(5 citation statements)

References 155 publications

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“…M channels were found to have strong influence over E rest , as both inhibition and enhancement of M channels caused ∼10 mV de- or hyperpolarization, respectively. M channels are physiologically inhibited by G q/11 -coupled protein-coupled receptors (GPCR) such as M 1 mAChR, bradykinin B 2 , protease activated receptor-2, and angiotensin II AT 1 , and such inhibition results in depolarization and increased firing (reviewed in [26,40,105] ). In contrast, some G i/o -coupled GPCR, such as somatostatin receptors, increase M current [87,98] .…”

Section: Discussionmentioning

confidence: 99%

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

Hao

Gigout

et al. 2014

Pain

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115

155

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Section: Discussionmentioning

confidence: 99%

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

Hao

Gigout

et al. 2014

Pain

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115

155

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“…DAG can activate protein kinase C (PKC) or produce other second messengers such as phosphotidic or arachidonic acids (e.g. via phospholipase A 2 activation) while IP 3 can induce release of Ca 2+ from IP 3 -sensitive Ca 2+ stores thereby mediating a large variety of Ca 2+ -dependent processes [13,55,128]. Particularly important for nociceptive signaling is the route of the G q -PLC pathway which leads to the activation of PKC as many sensory ion channels were shown to be sensitised through this pathway [98,114]; however, the PIP 2 -IP 3 -Ca 2+ route has also been implicated in inflammatory pain [86] (also see below).…”

Section: Inflammatory Mediators Their Receptors and Signalling Cascadesmentioning

confidence: 99%

“…One particular family of K + channels that plays a key role in controlling excitability of sensory neurons is the KCNQ (Kv7) family of channels, also known as 'M channels' [40, 86,113]. These slowlyactivating, non-inactivating K + channels with a very negative threshold voltage for activation are particularly well suited for controlling neuronal excitability as a fraction of these channels remain open near the resting membrane potential (reviewed in [46,128]). These channels are inhibited by the PLC-coupled receptors via both the depletion of PIP 2 (which they require as a co-factor to maintain activity) [84,136,155] and by IP 3 -mediated rises in cytosolic Ca 2+ [53,54].…”

Section: Ion Channels Underlying Hyperalgesia and Allodyniamentioning

confidence: 99%

“…As briefly mentioned above, the M channels (coded for by the KCNQ1-5 genes) conduct slow-kinetic, non-inactivating K + currents with a threshold for activation below −60 mV, allowing a fraction of these channels to remain open at or near the resting membrane potential of a neuron. It has been suggested that M current in neurons (including sensory) serves as an intrinsic voltage-clamp mechanism that controls the resting membrane potential, threshold for action potential firing and accommodation within trains of action potentials (reviewed in [46,128]). Inhibition of M current depolarises neurons making them more excitable, while augmentation has the opposite effect [56, 70,113,117,127].…”

Section: Ionic Mechanisms Of Spontaneous Painmentioning

confidence: 99%

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Understanding inflammatory pain: ion channels contributing to acute and chronic nociception

Linley

Rose

Ooi

et al. 2010

Pflugers Arch - Eur J Physiol

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117

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Inflammatory pain results from the increased excitability of peripheral nociceptive sensory fibres produced by the action of inflammatory mediators. This excitatory effect, in turn, is a result of the altered activity of ion channels within affected sensory fibres. This review will consider the molecular consequences of inflammation within the peripheral nerves with particular focus on the effects of different inflammatory mediators on the ion channels in sensory neurons. We will discuss the main signalling pathways triggered in neurons by inflammatory mediators; the ionic mechanisms underlying inflammatory hyperalgesia and spontaneous inflammatory pain and finally will briefly consider ion channels underlying pain in chronic inflammation.

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“…M‐type K + channels (KCNQ, Kv7) are important regulators of neuronal excitability because they control resting membrane potential and promote accommodation within bursts of action potentials in neurons that express them (reviewed by Delmas & Brown, 2005; Shapiro & Gamper, 2009). A general rule of thumb is that the inhibition of M channels in neurons is excitatory, while their activation has an anti‐excitatory, silencing effect.…”

Section: Introductionmentioning

confidence: 99%

M channel enhancers and physiological M channel block

Linley¹,

Pettinger²,

Huang³

et al. 2012

The Journal of Physiology

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Non-technical summary Specific membrane proteins called 'M channels' control the excitability of peripheral pain-sensing nerves. In certain disease conditions (e.g. inflammation), M channels become inhibited, and this contributes to the increased excitability of these nerves and, ultimately, to pain sensation. Recently, chemical compounds that enhance M channel activity have been discovered and were suggested as prospective analgesics. However, it was previously unknown whether these M channel enhancers could augment the activity of M channels that are inhibited in inflammatory conditions. We tested four compounds that possess M channel enhancer activity in various conditions mimicking inflammation. Our conclusions suggest that while the overall effect of the enhancers is reduced when M channels are inhibited, the remaining enhancement is sufficient to 'recover' M channel activity from inflammation-induced inhibition. Our results support pharmacological targeting of M channels in peripheral nerves as a strategy against inflammatory pain.Abstract M-type (Kv7, KCNQ) K + channels control the resting membrane potential of many neurons, including peripheral nociceptive sensory neurons. Several M channel enhancers were suggested as prospective analgesics, and targeting M channels specifically in peripheral nociceptors is a plausible strategy for peripheral analgesia. However, receptor-induced inhibition of M channels in nociceptors is often observed in inflammation and may contribute to inflammatory pain. Such inhibition is predominantly mediated by phospholipase C. We investigated four M channel enhancers (retigabine, flupirtine, zinc pyrithione and H 2 O 2 ) for their ability to overcome M channel inhibition via two phospholipase C-mediated mechanisms, namely depletion of membrane phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and a rise in intracellular Ca 2+ (an action mediated by calmodulin). Data from overexpressed Kv7.2/Kv7.3 heteromers and native M currents in dorsal root ganglion neurons suggest the following conclusions. (i) All enhancers had a dual effect on M channel activity, a negative shift in voltage dependence and an increase of the maximal current at saturating voltages. The enhancers differed in their efficacy to produce these effects. (ii) Both PIP 2 depletion and Ca 2+ /calmodulin strongly reduced the M current amplitude; however, at voltages near the threshold for M channel activation (−60 mV) all enhancers were able to restore M channel activity to a control level or above, while at saturating voltages the effects were more variable. (iii) Receptor-mediated inhibition of M current in nociceptive dorsal root ganglion neurons did not reduce the efficacy of retigabine or flupirtine to hyperpolarize the resting membrane potential. In conclusion, we show that all four M channel enhancers tested could overcome both PIP 2 and Ca 2+ -calmodulin-induced inhibition of Kv7.2/7.3 at voltages close to the threshold for action potential firing (−60 mV) but generally had reduced efficacy at a saturating voltag...

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Regulation of Neuronal Ion Channels by G‐Protein‐Coupled Receptors in Sympathetic Neurons

Cited by 4 publications

References 155 publications

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

Understanding inflammatory pain: ion channels contributing to acute and chronic nociception

M channel enhancers and physiological M channel block

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