The CaV2.3 R-Type Voltage-Gated Ca2+ Channel in Mouse Sleep Architecture

Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

doi:10.5665/sleep.3652

Cited by 24 publications

(36 citation statements)

References 62 publications

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“…However, we observed an opposite effect [239]. Our sleep study in Ca v 2.3 -/- mice suggested that Ca v 2.3 VGCCs significantly modulate sleep parameters in rodents in a light-dark cycle dependent manner.…”

Section: Structure Function and Pharmacology Of Voltage-gated Ca2+ Cmentioning

confidence: 83%

Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

Wormuth¹,

Lundt²,

Henseler³

et al. 2016

TONEUJ

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Background:Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca2+ channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Cav2.1 P/Q-type and Cav3.2 T-type Ca2+ channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2.3 R-type Ca2+ channel which exhibits an intriguing role in ictogenesis and seizure propagation. Cav2.3 R-type voltage gated Ca2+ channels (VGCC) emerged to be important factors in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and cellular epileptiform activity, e.g. in CA1 neurons. They also serve as potential target for various antiepileptic drugs, such as lamotrigine and topiramate.Objective: This review provides a summary of structure, function and pharmacology of VGCCs and their fundamental role in cellular Ca2+ homeostasis. We elaborate the unique modulatory properties of Cav2.3 R-type Ca2+ channels and point to recent findings in the proictogenic and proneuroapoptotic role of Cav2.3 R-type VGCCs in generalized convulsive tonic–clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity.Conclusion:Development of novel Cav2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders.

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Section: Structure Function and Pharmacology Of Voltage-gated Ca2+ Cmentioning

confidence: 83%

Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

Wormuth¹,

Lundt²,

Henseler³

et al. 2016

TONEUJ

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“…Therefore, the prolonged REM sleep episodes might be homeostatically regulated by abnormally maintained NREM sleep episodes and the reductions in the attempts to enter REM sleep. However, contributions to these results by other brain regions, including the mesopontine nuclei and hypothalamic nuclei [42], that regulate REM sleep cannot be completely excluded because these brain regions express low levels of PLCβ4 and send inputs to the thalamus [43]. Therefore, further studies are needed to fully understand the observed changes in the REM sleep states.…”

Section: Discussionmentioning

confidence: 99%

The thalamic mGluR1-PLCβ4 pathway is critical in sleep architecture

et al. 2016

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The transition from wakefulness to a nonrapid eye movement (NREM) sleep state at the onset of sleep involves a transition from low-voltage, high-frequency irregular electroencephalography (EEG) waveforms to large-amplitude, low-frequency EEG waveforms accompanying synchronized oscillatory activity in the thalamocortical circuit. The thalamocortical circuit consists of reciprocal connections between the thalamus and cortex. The cortex sends strong excitatory feedback to the thalamus, however the function of which is unclear. In this study, we investigated the role of the thalamic metabotropic glutamate receptor 1 (mGluR1)-phospholipase C β4 (PLCβ4) pathway in sleep control in PLCβ4-deficient (PLCβ4−/−) mice. The thalamic mGluR1-PLCβ4 pathway contains synapses that receive corticothalamic inputs. In PLCβ4−/− mice, the transition from wakefulness to the NREM sleep state was stimulated, and the NREM sleep state was stabilized, which resulted in increased NREM sleep. The power density of delta (δ) waves increased in parallel with the increased NREM sleep. These sleep phenotypes in PLCβ4−/− mice were consistent in TC-restricted PLCβ4 knockdown mice. Moreover, in vitro intrathalamic oscillations were greatly enhanced in the PLCβ4−/− slices. The results of our study showed that thalamic mGluR1-PLCβ4 pathway was critical in controlling sleep architecture.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0276-5) contains supplementary material, which is available to authorized users.

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“…Ca v 2.3 +/− embryos (kindly provided by Richard J. Miller, Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, IL, [1]) were re-derived with C57BL/6J mice and maintained with random intra-strain mating obtaining all genotypes [2]. Exons 4–8 encoding the pore-lining domain neighboring transmembrane domains of Cacna1e were replaced with a neo-URA3 cassette via homologous recombination (Mouse Genome Informatics; MGI Ref.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…Subsequently, lysis was stopped by heating the samples to 95 °C for 15 min. Following brief centrifugation (30 s, 20,000x g ), isolated genomic DNA was used for PCR [2].…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…Amplified PCR products were loaded on a 1.5% agarose gel containing agarose in 0.5 X TBE buffer (pH 8.0) and 0.3 mg/l ethidium bromide placed in a gel electrophoresis chamber filled with 0.5 X TBE. PCR product visualization and genotype specification was done using DIANA Imaging software (Raytest, Germany) [2] (Fig. 1).…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

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Gender specific hippocampal whole genome transcriptome data from mice lacking the Ca v 2.3 R-type or Ca v 3.2 T-type voltage-gated calcium channel

et al. 2017

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Voltage-gated Ca2+ channels are of central relevance in mediating numerous intracellular and transcellular processes including excitation-contraction coupling, excitation secretion-coupling, hormone and neurotransmitter release and gene expression. The Cav2.3 R-type Ca2+ channel is a high-voltage activated channel which plays a crucial role in neurotransmitter release, long-term potentiation and hormone release. Furthermore, Cav2.3 R-type channels were reported to be involved in ictogenesis, epileptogenesis, fear behavior, sleep, pre-and postsynaptic integration and rhythmicity within the hippocampus. Cav3 T-type Ca2+ channels are low-voltage activated and also widely expressed throughout the brain enabling neurons to switch between different firing patterns and to modulate burst activity. Disruption of T-type Ca2+ current has been related to sleep disorders, epilepsy, Parkinson׳s disease, depression, schizophrenia and pain. Cav3.2 ablation was further attributed to elevated anxiety and hippocampal alterations resulting in impaired long-term potentiation and memory. Given the importance of Cav2.3 and Cav3.2 voltage-gated Ca2+ channels within the CNS, particularly the hippocampus, we collected gender specific microarray transcriptome data of murine hippocampal RNA probes using the Affymetrix Exon Expression Chip Mouse Gene 1.0 ST v1. Information presented here includes transcriptome data from Cav2.3+/+, Cav2.3+/−, Cav2.3−/−, Cav3.2+/+, Cav3.2+/− and Cav3.2−/− mice from both genders, the protocol and list of primers used for genotyping animals, the hippocampal RNA isolation procedure and quality controls.

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The CaV2.3 R-Type Voltage-Gated Ca2+ Channel in Mouse Sleep Architecture

Abstract: Low-voltage activated CaV2.3 R-type Ca(2+) channels in the thalamocortical loop and extra-thalamocortical circuitries substantially regulate rodent sleep architecture thus representing a novel potential target for pharmacological treatment of sleep disorders in the future.

Cited by 24 publications

References 62 publications

Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

The thalamic mGluR1-PLCβ4 pathway is critical in sleep architecture

Gender specific hippocampal whole genome transcriptome data from mice lacking the Ca v 2.3 R-type or Ca v 3.2 T-type voltage-gated calcium channel

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