FRSC

Central myelinated axons are injured in a variety of conditions including ischemia, trauma and neuroinflammation. Failure of ion pumping in compromised axons leads to Na overload and depolarization (for a recent review see Trapp & Stys, Lancet Neurol., 2009). As a result, several Na-coupled and electrogenic ion and molecular transporters are stimulated to operate in reverse modes, transporting substances in inappropriate directions leading to damaging accumulation of Ca and neurotransmitters. For instance Na-Ca exchangers load axons with toxic amounts of Ca, and voltage-gated Ca channels also contribute to intracellular Ca loading. Importantly, axons contain intracellular Ca stores that are released by depolarization: L-type Ca channels sense voltage changes across the axolemma and in turn activate ryanodine receptors on "axoplasmic reticulum", releasing toxic amounts of Ca from internal pools, in a manner very similar to "excitation-contraction coupling" Ca release in skeletal..

Primary location: Alberta Canada