Upregulation of Calbindin-D-28k immunoreactivity by excitatory amino acids.
Excessive or prolonged exposure to excitatory amino acids (EAA) are thought to be neurotoxic by altering calcium homeostasis. A protective role of Calbindin-D-28 k (Calbindin) has been postulated due to its capacity to buffer calcium. Calbindin is highly expressed in the Purkinje cells (PCs), of the cerebellar cortex. Changes of the Calbindin immunoreactivity (IR) by the EAA has been here investigated in cerebellar slices maintained in vitro. It was found that at low temperature, PCs are very slightly immunoreactive and therefore the experiments were done at 22 degrees C. The results show that Calbindin-IR increases in PCs exposed to the neurotoxic agonists, Kainic acid (KA) and AMPA as well as to glutamate (Glu), the endogenous EAA. The increase is very rapid and slowly reversible; is induced by excitatory and excitotoxic concentrations of the agonists; is independent of the calcium influx. While KA- and AMPA-induced Calbindin-IR is blocked by CNQX, the KA/AMPA receptor antagonist, Glu-induced Calbindin-IR is only slightly decreased by CNQX and AP5, the NMDA receptor antagonist. It is concluded that Calbindin-containing neurons can increase their calcium buffering capacity in response to EAA binding to specific receptors, the response being independent of, but concomitant to calcium influx.
Batini
C
C
Laboratoire de Physiologie de la Motricité, CNRS, Université Pierre et Marie Curie, CHU Pitiéptrière, Paris, France.
Guegan
M
M
Palestini
M
M
Thomasset
M
M
Vigot
R
R
D000818:Animals; D001667:Binding, Competitive; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D003080:Cold Temperature; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis*; D011689:Purkinje Cells / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D064030:S100 Calcium Binding Protein G / Q000032:analysis*; D015854:Up-Regulation / Q000187:drug effects
D064026:Calbindins; D002118:Calcium; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D007608:Kainic Acid; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D064030:S100 Calcium Binding Protein G