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Voltage-Gated Ca2+ Channel Mediated Ca2+ Influx in Epileptogenesis

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Book cover Calcium Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 740))

Abstract

Voltage- and ligand-gated ion channels are key elements in the etiopathogenesis of various forms of epilepsy. In this chapter, we present an overview of the functional implications of voltage-gated Ca2+ channels in modulating internal Ca2+ level fluctuations and generating ictiform/epileptiform cellular electrophysiological activity. A specific focus will be on the fascinating and evolving field of high-voltage activated (HVA) Non-L-type Cav2.3 R-type channels and low-voltage activated (LVA) Cav3.1–3.3 T-type Ca2+ channels in the genesis of plateau potentials and excessive rebound bursting. Plateau potentials have been characterised in the hippocampus and were shown to be triggered by Cav2.3 which subsequently activate CNG channels that mediate long-lasting plateaus. In the thalamocortical network, a complex ion channel armamentarium is involved in regulating a complex balance of burst and tonic mode activity. Recent findings point to an outstanding role of R- and T-type channels in both thalamocortical eurhythmia and pathophysiological ­aberrations. Thus, pharmacological modulation of voltage-gated Ca2+-channels might prove more and more important in treatment of neurological and psychiatric disorder such as schizophrenia, mania, dementia and epilepsy.

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Abbreviations

5-HT:

Serotonin

AED:

Antiepileptic drug

AHP:

Afterhyperpolarisation

CNS:

Central nervous system

DAG:

Diacyl glycerol

GAERS:

Genetic absence epilepsy rat from Strasbourg

HCN:

Hyperpolarization and cyclic-nucleotide gated non-specific cation

HVA:

High voltage activated

IC:

Inferior colliculus

IGEs:

Idiopathic generalized epilepsies

IP3:

Inositoltrisphosphat

lh:

Lethargic

LVA:

Low voltage activated

M:

Muscarinic receptor

PKA:

Protein kinase A

PKC:

Protein kinase C

PLC:

Phospholipase C

RTN:

Reticular thalamic nucleus

sAHP:

Slow afterhyperpolarisation

SRS:

Spontaneous recurrent seizures

stg:

Stargazer

SWD:

Spike-wave discharge

SWS:

Slow-wave sleep

tg:

Tottering mouse model

VGCCS:

Voltage-gated calcium channels

WAG/RiJ:

Wistar Albino Glaxo rats

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  1. Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany

    Magdalena Siwek MS, Christina Henseler, Karl Broich MD, Anna Papazoglou Ph.D. & Marco Weiergräber MD, Ph.D.

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  1. Magdalena Siwek MS
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  2. Christina Henseler
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    Md. Shahidul Islam

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Siwek, M., Henseler, C., Broich, K., Papazoglou, A., Weiergräber, M. (2012). Voltage-Gated Ca2+ Channel Mediated Ca2+ Influx in Epileptogenesis. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 740. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2888-2_55

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