Inhibition of Ca<sup>2+</sup>-activated large-conductance K<sup>+</sup> channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

Liu, Yu; Savtchouk, Iaroslav; Acharjee, Shoana; Liu, Siqiong June

doi:10.1152/jn.01107.2010

Cited by 19 publications

(14 citation statements)

References 36 publications

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“…We reasoned that increasing the spike duration would allow the depolarization to propagate further along the dendrites and thereby shift the dendritic GluA2 gradient towards more distal regions. Our recent study shows that application of the potassium channel blocker TEA increases the AP width in stellate cells and enhances Ca 2+ entry via voltage-gated Ca 2+ channels by 40% without changing the frequency of spontaneous APs, IPSCs and EPSCs (Liu et al, 2011). We therefore incubated cerebellar slices with TEA (1 mM).…”

Section: Resultsmentioning

confidence: 99%

Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

et al. 2016

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Synaptic receptors gate the neuronal response to incoming signals, but they are not homogeneously distributed on dendrites. A spatially defined receptor distribution can preferentially amplify certain synaptic inputs, resize receptive fields of neurons, and optimize information processing within a neuronal circuit. Thus a longstanding question is how the spatial organization of synaptic receptors is achieved. Here we find that action potentials provide local signals that influence the distribution of synaptic AMPA receptors along dendrites in mouse cerebellar stellate cells. Graded dendritic depolarizations elevate CPEB3 protein at proximal dendrites where we suggest that CPEB3 binds to GluA2 mRNA suppressing GluA2 protein synthesis leading to a distance-dependent increase in synaptic GluA2 AMPARs. The activity-induced expression of CPEB3 requires increased Ca2+ and PKC activation. Our results suggest a cell-autonomous mechanism where sustained postsynaptic firing drives graded local protein synthesis thus directing the spatial organization of synaptic AMPARs.

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Section: Resultsmentioning

confidence: 99%

Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

et al. 2016

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“…The reduced external Ca 2+ would also be expected to suppress Ca 2+ -activated K + current [15]. The following two kinetically distinct Kv currents were isolated by the biophysical analysis and pharmacological approaches described in previous studies: I A and I K [20,21].…”

Section: Methodsmentioning

confidence: 99%

Hydrogen Sulfide Increases Excitability through Suppression of Sustained Potassium Channel Currents of Rat Trigeminal Ganglion Neurons

et al. 2013

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BackgroundHydrogen sulfide (H2S), an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However, the role and mechanism for H2S in nociceptive processing in trigeminal ganglion (TG) neuron remains unknown. The aim of this study is to investigate distribution of endogenous H2S synthesizing enzyme cystathionine-β-synthetase (CBS) expression and role of H2S on excitability and voltage-gated potassium channels of TG neurons.MethodsImmunofluorescence studies were carried out to determine whether CBS was co-expressed in Kv1.1 or Kv1.4-positive TG neurons. Whole cell patch clamp recordings were employed on acutely isolated TG neurons from adult male Sprague Dawley rats (6–8 week old). von Frey filaments were used to examine the pain behavioral responses in rats following injection of sodium hydrosulfide.ResultsIn rat TG, 77.3±6.6% neurons were immunoreactive for CBS, 85.1±3.8% for Kv1.1 and 97.8±1.1% for Kv1.4. Double staining showed that all CBS labeled cells were Kv1.1 and Kv1.4 positive, but only 92.2±6.1% of Kv1.1 and 78.2±9.9% of Kv1.4 positive cells contained CBS. Application of H2S donor NaHS (250 μM) led to a significant depolarization of resting membrane potential recorded from TG neurons. NaHS application also resulted in a dramatic reduction in rheobase, hyperpolarization of action potential threshold, and a significant increase in the number of action potentials evoked at 2X and 3X rheobase stimulation. Under voltage-clamp conditions, TG neurons exhibited transient A-type (IA) and sustained outward rectifier K+ currents (IK). Application of NaHS did suppress IK density while did not change IA density of TG neurons (n=6). Furthermore, NaHS, a donor of hydrogen sulfide, produced a significant reduction in escape threshold in a dose dependent manner.ConclusionThese data suggest that endogenous H2S generating enzyme CBS was co-localized well with Kv1.1 and Kv1.4 in TG neurons and that H2S produces the mechanic pain and increases neuronal excitability, which might be largely mediated by suppressing IK density, thus identifying for the first time a specific molecular mechanism underlying pain and sensitization in TG.

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“…The reduced external Ca 2+ would also be expected to suppress Ca 2+ -activated K + current [23]. The following two kinetically distinct Kv currents were isolated by the biophysical analysis and pharmacological approaches described in previous studies: I A and I K [15,24,25].…”

Section: Methodsmentioning

confidence: 99%

Upregulation of Cystathionine-β-Synthetase Expression Contributes to Inflammatory Pain in Rat Temporomandibular Joint

Miao

Meng

et al. 2014

Mol Pain

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BackgroundHydrogen sulfide (H2S), an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However, the role for H2S in nociceptive processing in trigeminal ganglion (TG) neuron remains unknown. The aim of this study was designed to investigate whether endogenous H2S synthesizing enzyme cystathionine-β-synthetase (CBS) plays a role in inflammatory pain in temporomandibular joint (TMJ).MethodsTMJ inflammatory pain was induced by injection of complete Freund’s adjuvant (CFA) into TMJ of adult male rats. Von Frey filaments were used to examine pain behavioral responses in rats following injection of CFA or normal saline (NS). Whole cell patch clamp recordings were employed on acutely isolated TG neurons from rats 2 days after CFA injection. Western blot analysis was carried out to measure protein expression in TGs.ResultsInjection of CFA into TMJ produced a time dependent hyperalgesia as evidenced by reduced escape threshold in rats responding to VFF stimulation. The reduced escape threshold was partially reversed by injection of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, in a dose-dependent manner. CFA injection led to a marked upregulation of CBS expression when compared with age-matched controls. CFA injection enhanced neuronal excitability as evidenced by depolarization of resting membrane potentials, reduction in rheobase, and an increase in number of action potentials evoked by 2 and 3 times rheobase current stimulation and by a ramp current stimulation of TG neurons innervating the TMJ area. CFA injection also led to a reduction of IK but not IA current density of TG neurons. Application of AOAA in TMJ area reduced the production of H2S in TGs and reversed the enhanced neural hyperexcitability and increased the IK currents of TG neurons.ConclusionThese data together with our previous report indicate that endogenous H2S generating enzyme CBS plays an important role in TMJ inflammation, which is likely mediated by inhibition of IK currents, thus identifying a specific molecular mechanism underlying pain and sensitization in TMJ inflammation.

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Inhibition of Ca²⁺-activated large-conductance K⁺ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

Abstract: Liu Y, Savtchouk I, Acharjee S, Liu SJ. Inhibition of Ca 2ϩ -activated large-conductance K ϩ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells.

Cited by 19 publications

References 36 publications

Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

Hydrogen Sulfide Increases Excitability through Suppression of Sustained Potassium Channel Currents of Rat Trigeminal Ganglion Neurons

Upregulation of Cystathionine-β-Synthetase Expression Contributes to Inflammatory Pain in Rat Temporomandibular Joint

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Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

Abstract: Liu Y, Savtchouk I, Acharjee S, Liu SJ. Inhibition of Ca 2ϩ -activated large-conductance K ϩ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells.

Cited by 19 publications

References 36 publications

Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

Hydrogen Sulfide Increases Excitability through Suppression of Sustained Potassium Channel Currents of Rat Trigeminal Ganglion Neurons

Upregulation of Cystathionine-β-Synthetase Expression Contributes to Inflammatory Pain in Rat Temporomandibular Joint

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Inhibition of Ca²⁺-activated large-conductance K⁺ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells