Alteration of neuronal calcium homeostasis and excitotoxic vulnerability by chronic depolarization.
Free intracellular Ca2+ concentration ([Ca2+]i, Ca2+ currents, and excitatory amino acid (EAA) currents were studied in spinal neurons cultured in low (4.5 mM) and high (25 mM) extracellular potassium. When challenged with lethal concentrations of N-methyl-D-aspartate (NMDA) or kainate, neurons cultured in 25 mM K+ exhibited markedly attenuated Ca2+ currents and [Ca2+]i responses, and survived the EAA challenge more readily than controls. Surprisingly, NMDA and Kainate currents remained comparable between neurons grown in high- and low K+. The disparity between the observed [Ca2+]i increases and EAA currents suggests that chronic depolarization induces a fundamental alteration in intracellular Ca2+ handling. This phenomenon may provide clues for the development of neuroprotective strategies against excitotoxin excess.
Tymianski
M
M
Playfair Neuroscience Unit, Toronto Hospital, Ont., Canada.
Wang
L Y
LY
MacDonald
J F
JF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D018846:Excitatory Amino Acids / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
D015220:Calcium Channels; D018846:Excitatory Amino Acids; D002118:Calcium