ALTERATION OF NEURONAL CALCIUM HOMEOSTASIS AND EXCITOTOXIC VULNERABILITY BY CHRONIC DEPOLARIZATION

Free intracellular Ca2+ concentration ([Ca2+](i), Ca2+ currents, and e xcitatory amino acid (EAA) currents were studied in spinal neurons cul tured in low (4.5 mM) and high (25 mM) extracellular potassium. When c hallenged with lethal concentrations of N-methyl-D-aspartate (NMDA) or kainate, neurons cultured in 25 mM K+ exhibited markedly attenuated C a2+ currents and [Ca2+](i) responses, and survived the EAA challenge m ore readily than controls. Surprisingly, NMDA and Kainate currents rem ained comparable between neurons grown in high- and low K+. The dispar ity between the observed [Ca2+](i) increases and EAA currents suggests that chronic depolarization induces a fundamental alteration in intra cellular Ca2+ handling. This phenomenon may provide clues for the deve lopment of neuroprotective strategies against excitotoxin excess.