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The Journal of Neuroscience, March 1, 2000, 20(5):1831-1836
Surviving Granule Cells of the Sclerotic Human Hippocampus Have
Reduced Ca2+ Influx Because of a Loss of
Calbindin-D28k in Temporal Lobe Epilepsy
U. Valentin
Nägerl1,
Istvan
Mody1,
Monika
Jeub2,
Ailing A.
Lie2,
Christian E.
Elger2, and
Heinz
Beck2
1 Department of Neurology and Physiology, University of
California at Los Angeles School of Medicine, Los Angeles, California
90095, and 2 Department of Epileptology, University of Bonn
Medical Center, D-53105 Bonn, Germany
In mesial temporal lobe epilepsy (mTLE), the predominant form of
epilepsy in adults, and in animal models of the disease, there is a
conspicuous loss of the intracellular Ca2+-binding
protein calbindin-D28k (CB) from granule cells (GCs) of the
dentate gyrus. The role of this protein in nerve cell function is
controversial, but here we provide evidence for its role in controlling
Ca2+ influx into human neurons. In patients with
Ammon's horn sclerosis (AHS), the loss of CB from GCs markedly
increased the Ca2+-dependent inactivation of
voltage-dependent Ca2+ currents
(ICa), thereby diminishing
Ca2+ influx during repetitive neuronal firing.
Introducing purified CB into GCs restored Ca2+
current inactivation to levels observed in cells with normal CB content
harvested from mTLE patients without AHS. Our data are consistent with
the possibility of neuroprotection secondary to the CB loss. By
limiting Ca2+ influx through an enhanced
Ca2+-dependent inactivation of voltage-dependent
Ca2+ channels during prolonged neuronal discharges,
the loss of CB may contribute to the resistance of surviving human
granule cells in AHS.
Key words:
Ammon's horn sclerosis; mesial temporal lobe epilepsy; granule cells; voltage-dependent Ca2+ currents; calcium channels; calbindin-D28k
Copyright © 2000 Society for Neuroscience 0270-6474/00/2051831-06$05.00/0
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