Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3055562 | Experimental Neurology | 2013 | 9 Pages |
CNS white matter, the collection of axons and supporting glia of the mammalian CNS, makes up close to 50% of the human brain by volume. Interruption of vital interconnects within this tissue, even over a short segment, often leads to serious morbidity in a broad range of neurological disorders. Axons, glia and myelin express a complex array of conventional voltage gated ion channels, intracellular Ca2 + release channels, neurotransmitter uptake and release mechanisms, together with matching transmitter receptors. Dysregulation of ion homeostasis induced by injury or energy failure leads to depolarization and intracellular Na+ accumulation, which in turn triggers inappropriate ion translocation (i.e. Ca2 + influx) and transmitter release; together these events further promote more Ca2 + influx, while at the same time triggering even more toxic Ca2 + release from intracellular Ca2 + stores. Uncontrolled intracellular Ca2 + increases overactivate a variety of Ca2 +-sensitive enzyme systems culminating in permanent injury to axon, myelin and glia.