Review: Cav2.3 R-type Voltage-Gated Ca(2+) Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity.

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Wormuth C, Lundt A, Henseler C, Muller R, Broich K, Papazoglou A, Weiergraber M

Review: Cav2.3 R-type Voltage-Gated Ca(2+) Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity.

Open Neurol J. 2016 Sep 30;10:99-126. doi: 10.2174/1874205X01610010099. eCollection 2016.

PubMed ID

27843503 [ View in PubMed

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Abstract

BACKGROUND: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca(2+) 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 Ca(2+) channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2.3 R-type Ca(2+) channel which exhibits an intriguing role in ictogenesis and seizure propagation. Cav2.3 R-type voltage gated Ca(2+) 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 Ca(2+) homeostasis. We elaborate the unique modulatory properties of Cav2.3 R-type Ca(2+) 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Topiramate	Voltage-dependent R-type calcium channel (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details