Intrinsische Plastizität nach Status Epilepticus durch Regulation spannungsabhängiger Ionenkanäle

Zeitschrift für Epileptologie 01/2003; 16(3):243-249. DOI: 10.1007/s10309-003-0030-8


While a multitude of studies have dissected
epilepsy-related changes in synaptic communication between
neurons, alterations in intrinsic firing properties and their
cellular mechanisms have received only minor attention.
Here we summarize findings suggesting that intrinsic
properties of hippocampal neurons may be dramatically modified
during epileptogenesis. We have recently shown that CA1
pyramidal neurons in epileptic tissue show an increased
propensity to generate intrinsic burst discharges that most
probably rely on altered voltage-dependent
Ca2+ channels (VDCCs). Our further
experiments suggest that the mechanism underlying increased
Ca2+-dependent bursting is the
up-regulation of a T-type Ca2+
channel in CA1 neurons, most probably mediated by the
Cav 3.2 subunit. The change in intrinsic
properties strongly augment the input-output properties of CA1
neurons to synaptic stimulation. Furthermore, several lines of
evidence indicated that these bursting neurons may be important
for initiation of seizures.
Investigating the up-regulation of specific VDCC subtypes
in experimental and human TLE will further our understanding of
the molecular mechanisms involved in the initiation of seizures
in this disorder. It is hoped that such an understanding will
trigger the design of novel antiepileptic drugs specifically
targeted to pathologically altered VDCCs, which might be
effective in the treatment of currently refractory TLE.

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