Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death - PubMed (original) (raw)
Changes in [Ca2+]i after exposure to AMPA, kainate, NMDA, or high KCl at normal and acidic pH. Refer to Table 3for corresponding calcium integral measurements. All measurements were performed at 24°C. A, AMPA response; sequential averaged changes in [Ca2+]i in 35 neurons during and after a 5 sec exposure to 10 μ
m
AMPA plus 100 μ
m
cyclothiazide and 10 μ
m
MK-801 at pH 7.4 or 6.6. Exposure to acidic pH attenuates peak AMPA responses but impairs recovery. B, Kainate-induced [Ca2+]i responses at pH 7.4 and 6.6 were similar to that observed for AMPA. Cultures were exposed to 100 μ
m
kainate, as outlined in A. Peak responses are attenuated at pH 6.6, but again, normalization was markedly impaired. C, Reducing extracellular pH attenuates the peak [Ca2+]i response to NMDA with minimal change in subsequent normalization. The trace represents average (n = 27 neurons) changes in [Ca2+]i during and after 5 sec exposures to 50 μ
m
NMDA at pH 7.4 or 6.6. In the low pH exposure experiments, neurons were washed for 5 min at pH 6.6 before the application of NMDA, exposed to NMDA at pH 7.4 for 5 sec, and immediately returned at pH 6.6 for 15 min. Under these conditions the intracellular pH remains below 6.6, and the brief extracellular exposure to NMDA at pH 7.4 allows activation of NMDA receptors (i.e., the pH-sensitive site on NMDA receptors is extracellular). D, Reducing extracellular pH attenuates the peak [Ca2+]i response to high KCl with minimal change in subsequent normalization. The_trace_ represents average (n = 30 neurons) changes in [Ca2+]i during and after 5 sec exposures to 60 m
m
KCl plus 10 μ
m
MK-801 at pH 7.4 or 6.6. In the low pH exposure experiments, neurons were washed for 5 min at pH 6.6 before the application of 60 m
m
KCl, exposed to high KCl at pH 7.4, and immediately returned to pH 6.6 for 15 min. Under these conditions, the intracellular pH remains below 6.6, and the brief extracellular exposure to 60 m
m
KCl at pH 7.4 allows activation of voltage-sensitive calcium channels. All the experiments are representative of at least three different experiments in three different cultures.