Craner, et al. (2003). Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger...
• Craner MJ, Hains BC, Lo AC, Black JA and Waxman SG (2003). Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain. Department of Neurology and PVA/EPVA Center for Neuroscience Research, Yale University School of Medicine, New Haven, and Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, Connecticut, USA. Axonal degeneration contributes to the development of non-remitting neurological deficits and disability in multiple sclerosis, but the molecular mechanisms that underlie axonal loss in multiple sclerosis are not clearly understood. Studies of white matter axonal injury have demonstrated that voltage-gated sodium channels can provide a route for sodium influx into axons that triggers reverse operation of the Na(+)/Ca(2+) exchanger (NCX) and subsequent influx of damaging levels of intra-axonal calcium. The molecular identities of the involved sodium channels have, however, not been determined. We have previously demonstrated extensive regions of diffuse expression of Nav1.6 and Nav1.2 sodium channels along demyelinated axons in experimental allergic encephalomyelitis (EAE). Based on the hypothesis that the co-localization of Nav1.6 and NCX along extensive regions of demyelinated axons may predispose these axons to injury, we examined the expression of myelin basic protein, Nav1.2, Nav1.6, NCX and beta-amyloid precursor protein (beta-APP), a marker of axonal injury, in the spinal cord dorsal columns of mice with EAE. We demonstrate a significant increase in the number of demyelinated axons demonstrating diffuse Nav1.6 and Nav1.2 sodium channel immunoreactivity in EAE (92.2 +/- 2.1% of beta-APP positive axons were Nav1.6-positive). Only 38.0 +/- 2.9% of beta-APP positive axons were Nav1.2 positive, and 95% of these co-expressed Nav1.6 together with Nav1.2. Using triple-labelled fluorescent immunohistochemistry, we demonstrate that 73.5 +/- 4.3% of beta-APP positive axons co-express Nav1.6 and NCX, compared with 4.4 +/- 1.0% in beta-APP negative axons. Our results indicate that co-expression of Nav1.6 and NCX is associated with axonal injury in the spinal cord in EAE.
>Studies of white matter axonal injury have
demonstrated that voltage-gated sodium channels can provide a
route for sodium influx into axons that triggers reverse
operation of the Na(+)/Ca(2+) exchanger (NCX) and subsequent
influx of damaging levels of intra-axonal calcium.<
What is the Na(+)/Ca(2+) exchanger (NCX)?
Frank, neurons (and their axons) possess Na:Ca exchangers, a membrane protein that exchanges Na and Ca ions across the membrane. Normally, the inside of cells have very low calcium ionic activity (about 70 nanomolar compared to 1.2 millimolar extracellular levels). The inside of cells contain about 30 millimolar concentration.
Let me give you the technical explanation and you can ask more queestions if you don't understand. There is a Ca pump but this pump tends to be slow and energy intensive. So, the cell uses the Na gradient as the energy source to drive calcium efflux from the axons. Unfortunately, when the cells take on lots of sodium, this pump reverses and paradoxically allows more calcium influx.
There are specific Ca:Na exchanger blockers and several studies have shown that these may be neuroprotective in spinal cord injury.
New Key to Tissue Regeneration: Drug Treatment Triggers Sodium Ions to Regrow . . .
New Key to Tissue Regeneration: Drug Treatment Triggers Sodium Ions to Regrow Nerves and Muscle
"The Tufts scientists have found a way to regenerate injured spinal cord and muscle
by using small molecule drugs to trigger an influx of sodium ions into injured cells."
"The ability to restore regeneration using a temporally-controllable pharmacological approach
not requiring gene therapy is extremely exciting," said the researchers."
"Amphibians such as frogs can restore organs lost during development, including the lens and tail.
The frog tail is a good model for human regeneration because it repairs injury in the same way that people do: each tissue
makes more of itself."
Science Daily (Sep. 29, 2010) – Sodium gets a bad rap for contributing to hypertension and cardiovascular disease. Now biologists at Tufts University's School of Arts and Sciences have discovered that sodium also plays a key role in initiating a regenerative response after severe injury. The Tufts scientists have found a way to regenerate injured spinal cord and muscle by using small molecule drugs to trigger an influx of sodium ions into injured cells.
Read more http://www.sciencedaily.com/releases...0928171428.htm