The Ca(v)2.3 voltage-gated calcium channel in epileptogenesis--shedding new light on an enigmatic channel.
The Ca(v)2.3 encoded Ca2+ channel is probably one of the least well-understood voltage-gated calcium channels in terms of physiology, pharmacology and clinical relevance. Here we provide a detailed insight into the functional involvement of Ca(v)2.3 in etiology and pathogenesis of both convulsive and non-convulsive seizures. In the CNS, Ca(v)2.3 containing E/R-type Ca2+ channels are involved in triggering epileptiform discharges by significantly contributing to plateau potentials and afterdepolarisations. Pharmacological analysis further revealed that various antiepileptic drugs specifically target Ca(v)2.3 VGCCs capable of blocking epileptiform burst activity. Whereas electroencephalographic recordings in Ca(v)2.3-/- mice did not reveal any ictal-like discharges, seizure susceptibility was dramatically reduced in Ca(v)2.3-/- animals compared to controls, further supporting the observation that Ca(v)2.3 is an important factor in triggering epileptiform activity in neuronal populations. Although some aspects of its relationship to epilepsy have been uncovered, further functional characterization of Ca(v)2.3 in etiology and pathogenesis of human epileptic syndromes as well as development of new antiepileptic drugs specifically targeting Ca(v)2.3 turns out to become indispensable.
Weiergräber
Marco
M
Institute for Neurophysiology, University of Cologne, Robert-Koch-Str. 39, D 50931 Cologne, Germany. akp74@uni-koeln.de
Kamp
Marcel A
MA
Radhakrishnan
Kayalvizhi
K
Hescheler
Jürgen
J
Schneider
Toni
T
D000818:Animals; D020908:Calcium Channels, R-Type / Q000502:physiology*; D027682:Cation Transport Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D006801:Humans
C423009:CACNA1E protein, human; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins