Effects of depolarizing stimuli on calcium homeostasis in cultured rat motoneurones.
Intracellular calcium concentrations in individual rat motoneurones in enriched primary cultures were measured by Indo-1 fluorimetry. Motoneurones in the cultures were characterized morphometrically and by cholineacetyltransferase immunocytochemistry. Depolarization of the cells with glutamic acid or veratridine increased intracellular calcium levels, which returned to baseline only slowly after removal of the depolarizing agent. The use of selective agonists (N-methyl-D-aspartic acid, AMPA, kainic acid, quisqualic acid and 1R-3S-ACPD) and antagonists (MK 801 and CNQX) showed that the excitatory amino acid-evoked responses were mediated by AMPA/kainate receptors rather than by NMDA receptors. Depolarization-evoked calcium transients in motoneurones are blocked by the neuroprotective drug riluzole Calcium transients reflected entry of calcium from without the cell, and their blockade by nitrendipine and lanthanum chloride suggested that this entry took place primarily through voltage-dependent calcium channels. These findings may be relevant for understanding the selective vulnerability of motoneurones to excitotoxicity in amyotrophic lateral sclerosis, and the therapeutic activity of riluzole in the treatment of this disease.
Hubert
J P
JP
Pharmaceutical Research Department, Rhône-Poulenc Rorer SA, Vitry-sur-Seine, France.
Burgevin
M C
MC
Terro
F
F
Hugon
J
J
Doble
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006706:Homeostasis; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014701:Veratridine / Q000494:pharmacology
D018698:Glutamic Acid; D014701:Veratridine; D002118:Calcium