Studies dating to the mid 1980s indicate that excessive excitation of neurons
results in cell death (e.g., Reference 180). More recently, this death has been
compared and contrasted to neurotrophin withdrawal-induced PCD. Model
systems that demonstrate this “excitotoxic” effect include various neuronal
cells exposed to glutamate, the glutamate analog N-methyl-D-aspartate
(NMDA), potassium ionophores like valinomycin, calcium channel blockers
(e.g., nifedipine or verapimil),181 low calcium medium, or 3-nitropropionic
acid.182 In addition, it has been observed that survival of cultured cerebellar
granule neurons beyond the first 5 days in vitro is enhanced when the cells
are maintained in depolarizing concentrations of potassium (20 to 25 mM).183
Conversely, transfer of these neurons to nondepolarizing medium (5 mM
potassium) results in apoptotic cell death,157 providing one of the more
widely utilized models of neuronal PCD.