Calcium Signaling pp 1219-1247

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

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

  • Magdalena Siwek
  • Christina Henseler
  • Karl Broich
  • Anna Papazoglou
  • Marco Weiergräber
Chapter

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.

Keywords

Epilepsy Hippocampus Plateau potentials Rebound burst firing Voltage-gated Ca2+ channels 

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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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Magdalena Siwek
    • 1
  • Christina Henseler
    • 1
  • Karl Broich
    • 1
  • Anna Papazoglou
    • 1
  • Marco Weiergräber
    • 1
  1. 1.Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM)BonnGermany

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