Further characterization of regulation of Ca<sub>V</sub>2.2 by Stargazin

Tselnicker, Isabella; Dascal, Nathan

doi:10.4161/chan.4.5.13504

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…Stargazin can act as either a voltage-gated calcium channel subunit or an AMPAR auxiliary subunit (Letts, 2005; Osten and Stern-Bach, 2006; Tselnicker and Dascal, 2010) and its mutation in stg leads to suppression of AMPAR-mediated synaptic excitation in cerebellum (Chen et al, 2000) and RTN (Menuz and Nicoll, 2008), along with increased VB tonic inhibition (Cope et al, 2009). Absence seizures require RTN (Avanzini et al, 1992) and epileptiform network activity depends on RTN excitation to either sustain intrathalamic (von Krosigk et al, 1993; Bal and McCormick, 1993; Huguenard and Prince, 1994; Warren and Jones, 1994) or enhance thalamocortical (Blumenfeld and McCormick, 2000; Bal et al, 2000) seizure-related activity.…”

Section: Discussionmentioning

confidence: 99%

Enhanced NMDA Receptor-Dependent Thalamic Excitation and Network Oscillations in Stargazer Mice

et al. 2012

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Disturbances in corticothalamic circuitry can lead to absence epilepsy. The reticular thalamic nucleus (RTN) plays a pivotal role in that it receives excitation from cortex and thalamus, and when strongly activated can generate excessive inhibitory output and epileptic thalamocortical oscillations that depend on post-inhibitory rebound. Stargazer mice (stg) have prominent absence seizures resulting from a mutant form of the AMPAR auxiliary protein stargazin. Reduced AMPAR excitation in RTN has previously been demonstrated in stg, yet the mechanisms leading from RTN hypoexcitation to epilepsy are unknown and unexpected, as thalamic epileptiform oscillatory activity requires AMPARs. We demonstrate hyperexcitability in stg thalamic slices and further characterize the various excitatory inputs to RTN using electrical stimulation and laser scanning photostimulation. Patch-clamp recordings of spontaneous and evoked EPSCs in RTN neurons demonstrate reduced amplitude and increased duration of the AMPAR-component with an increased amplitude NMDAR-component. Short 200 Hz stimulus trains evoked a gradual ~3-fold increase in NMDAR EPSCs compared to single stimuli in wild-type (wt), indicating progressive NMDAR recruitment, whereas in stg cells, NMDAR responses were nearly maximal with single stimuli. Array tomography revealed lower synaptic, but higher perisynaptic, AMPAR density in stg RTN. Increasing NMDAR activity via reduced [Mg2+]o in wt phenocopied the thalamic hyperexcitability observed in stg, while changing [Mg2+]o had no effect on stg slices. These findings suggest that, in stg, a trafficking defect in synaptic AMPARs in RTN cells leads to a compensatory increase in synaptic NMDARs, and enhanced thalamic excitability.

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Section: Discussionmentioning

confidence: 99%

Enhanced NMDA Receptor-Dependent Thalamic Excitation and Network Oscillations in Stargazer Mice

et al. 2012

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“…Hence, it may be reasonable to expect a similar trafficking function for neuronal calcium channels. However, most coexpression studies involving different types of c subunits have revealed relatively subtle effects on channel function [77,[83][84][85]. One notable exception is c7, which dramatically reduces N-type current density in transient expression systems [86].…”

Section: Cava2d Regulation Of Hva Channel Membrane Traffickingmentioning

confidence: 99%

Trafficking and stability of voltage-gated calcium channels

Simms

Zamponi

2011

Cell. Mol. Life Sci.

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Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and internalization of this important ion channel family.

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Further characterization of regulation of Ca_V2.2 by Stargazin

Cited by 2 publications

References 16 publications

Enhanced NMDA Receptor-Dependent Thalamic Excitation and Network Oscillations in Stargazer Mice

Enhanced NMDA Receptor-Dependent Thalamic Excitation and Network Oscillations in Stargazer Mice

Trafficking and stability of voltage-gated calcium channels

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Further characterization of regulation of CaV2.2 by Stargazin

Cited by 2 publications

References 16 publications

Enhanced NMDA Receptor-Dependent Thalamic Excitation and Network Oscillations in Stargazer Mice

Enhanced NMDA Receptor-Dependent Thalamic Excitation and Network Oscillations in Stargazer Mice

Trafficking and stability of voltage-gated calcium channels

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Further characterization of regulation of Ca_V2.2 by Stargazin