The most distinguishing feature of neurons is their capacity for regenerative electrical activity. This activity imposes a significant mitochondrial burden, especially in neurons that are autonomously active, have broad action potentials, and exhibit prominent Ca(2+) entry. Many of the genetic mutations and toxins associated with Parkinson's disease compromise mitochondrial function, providing a mechanistic explanation for the pattern of neuronal pathology in this disease. Because much of the neuronal mitochondrial burden can be traced to L-type voltage-dependent channels (channels for which there are brain-penetrant antagonists approved for human use), a neuroprotective strategy to reduce this burden is available.