Calcium extrusion protein expression in the hippocampal formation of chronic epileptic rats after kainate-induced status epilepticus.
OBJECTIVE
The plasma membrane Ca2+ -adenosine triphosphatase (ATPase) (PMCA) and (potassium-dependent) sodium-calcium exchange [NC(K)X] represent two main calcium-extrusion mechanisms that are important for the restoration of [Ca2+]i levels after electrical activity. We investigated whether the expression of these calcium-extrusion proteins is altered in the course of epileptogenesis.


METHODS
Hippocampal-parahippocampal protein expression of NCX1, 2, and 3, PMCA1-4, and NCKX2 at an early and late stage after kainate-induced status epilepticus (SE) was compared with that in control rats by using immunocytochemistry.


RESULTS
Several alterations were found in chronic epileptic rats: (a) NCX1 expression was permanently decreased in the inner molecular layer (IML) of the dentate gyrus (DG) and entorhinal cortex layer III (ECIII), related to neuronal loss in hilus and ECIII, respectively; (b) PMCA and NCKX2 expression was transiently upregulated in the IML, and decreased in several areas where cell loss had occurred, (c) NCX3 expression, which in control rats is abundant in presynaptic terminals of mossy fibers (MF), was extensively and permanently decreased in stratum lucidum and hilar region. In addition, newly formed MF sprouts that project to the DG iml did not noticeably express NCX3; (d) NCX2 and NCKX2 were (transiently) upregulated in astrocytes of epileptic rats throughout the hippocampal formation, including ECIII.


CONCLUSIONS
These region-specific changes in calcium-extrusion proteins reflect a change in calcium regulation. Whether these regional-specific changes of calcium-extrusion proteins are associated with an abnormal calcium homeostasis must be determined. Because some alterations of calcium-extrusion protein expression are already present at an early stage of epileptogenesis, they could be involved in this process.
Swammerdam Institute for Life Sciences, Section Neurobiology, University of Amsterdam, Amsterdam, The Netherlands.
Susan O M
SO
Ketelaars
Jan A
JA
Gorter
Eleonora
E
Aronica
Wytse J
WJ
Wadman
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D027682:Cation Transport Proteins; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D007608:Kainic Acid; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D027682:Cation Transport Proteins; D018690:Excitatory Amino Acid Agonists; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; C074530:potassium-dependent sodium-calcium exchanger; D053499:Plasma Membrane Calcium-Transporting ATPases; C506955:Atp2b1 protein, rat; D000252:Calcium-Transporting ATPases; D007608:Kainic Acid