Dual mechanisms of Ca(2+) increases elicited by N-methyl-D-aspartate in immature and mature cultured cortical neurons.
Cortical primary cultures were loaded with the fluorescent indicator fluo-3 for assessment of intracellular-free Ca(2+) ions with the aid of a confocal laser-scanning microscope. The addition of N-methyl-D-aspartic acid (NMDA) markedly increased the number of fluorescent cells in a manner sensitive to prevention by both an NMDA channel blocker and MgCl(2). In the absence of added MgCl(2), NMDA induced a sustained increase in the number of fluorescent cells with a transient increase by KCl in cells cultured for 3 days in vitro (DIV). Both nifedipine and dantrolene were more potent in preventing the increase by NMDA in cortical preparations cultured for 9 DIV than those for 3 DIV. These results suggest that activation of NMDA receptors may lead to a sustained increase in intracellular-free Ca(2+) concentrations in immature cultured neurons, in a manner less dependent on the influx through L-type voltage-dependent channels as well as the release from intracellular stores than in mature neurons.
Nakamichi
Noritaka
N
Division of Molecular Membrane Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
Ohno
Hiroshi
H
Kuramoto
Nobuyuki
N
Yoneda
Yukio
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D003620:Dantrolene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D015636:Magnesium Chloride / Q000494:pharmacology; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D007476:Ionophores; D008869:Microtubule-Associated Proteins; D009125:Muscle Relaxants, Central; D016194:Receptors, N-Methyl-D-Aspartate; D015636:Magnesium Chloride; D018698:Glutamic Acid; D016202:N-Methylaspartate; D011189:Potassium Chloride; D003620:Dantrolene; D002118:Calcium