NO is associated with the main excitatory neurotransmitter Glutamate and
the generation of action potentials in the nerves. Small amounts of it open up
the calcium ion channels of the nerves (along with glutamate, an excitatory
neurotransmitter) sending a strong excitatory impulse. Larger amounts of NO
can force the calcium channels to fire more rapidly which can lead to apoptosis
or programmed cell death. Thus NO mediates the neurotoxicity of glutamate
through the formation of cGMP by activation of glutamate receptors. As stated in
the section on Nitric Oxide, cGMP participates in signal transduction within the
nervous system.
In the brain a stimulus (such as glutamate) acting at NMDA receptors triggers
Ca2+ influx which binds to calmodulin, thereby activating NOS. This mode of
activation explains how glutamate neurotransmission stimulates NO formation in
a matter of seconds. In blood vessels, acetylcholine acting at muscarinic receptors
on endothelial cells activates the phosphoinositide cycle to generate Ca2+, which
stimulates NOS to produce NO for blood vessel dilatation.
The influx of Ca2+ into the neuron activates an enzyme called calcium-
calmodulin-dependent kinase II (CaMKII). Kinases attach phosphate groups to
proteins and altering their functioning. In this case, CaMKII phosphorylates a
second type of Glutamine receptor called amPa receptors, which makes them
more permeable to sodium ions (Na+) thus lowering the resting potential of the
cell and making it more sensitive to incoming impulses. In addition, there is
evidence that the activity of CaMKII increases the number of AMPA receptors at
the synapse.
ProtectinG GlUtamate recePtors
Studies found that alpha-lipoic acid improves memory in aged mice, probably
by a partial compensation of NMDA receptor deficits. It is thought that its free
radical scavenger properties preserve the cell membrane and so protect loss of
NMDA receptors. It also protects membranes and receptors through improved
sugar and insulin metabolism. Alpha lipoic acid is a unique antioxidant because
it prevents and may even reverse the attachment of sugar to protein, a process
known as glycation or crosslinking. Alpha lipoic protects cells from AGEs by
allowing better metabolism of sugar in the cell, this prevents its buildup and also
by allowing the body’s natural repair mechanisms to work better.
A team of researchers led by Bruce N. Ames, professor of molecular and cell
biology at UC Berkeley, fed older rats acetyl-L-carnitine and alpha-lipoic acid.
They found that the combination of the two supplements effectively reduce aging
by tuning up the mitochondria, rejuvenating and energizing cells and both spatial
and temporal memory, and reduced the amount of oxidative damage to RNA in
the brain’s hippocampus, an area important in memory. It is advisable therefore
for those undergoing kundalini to take L-carnitine and alpha-lipoic supplements
as well as adopt a low glycemic diet.
Apparently the glutamate receptors in the brains of drug addicts retreat into the
cell membrane, perhaps to try and prevent the cell from becoming over stimulated