Could Anyone Help Me Attain a Better Understanding of Ion Channels?

[SpunkySkunk347]

As it is theorized among stimulant users, magnesium supplements can be an essential tool for avoiding muscle tension as well as stimulant-induced compulsions (teeth grinding, etc)..

From what I understand, the magnesium will make it harder for an action potential to be generated by neurons using calcium/magnesium ion channels. Am I correct? Or is that not the right way of viewing/wording it?


Are calcium/magnesium ion channels more prevalent in CNS pathways that dictate muscle control and impulse? Or are they perhaps more prevalent in the peripheral nervous system?

How do calcium/magnesium ion channels differ from other types of ion channels when it comes to which regions they are more prevalent in in the brain, and what are some of the functions of neural pathways with prevalently higher amounts of a other types of ion channels?


How does our body utilize the magnesium from a magnesium supplement? How does it "end up where it needs to be" in the ion channels of CNS neurons from our digestive tract? If it merely floats around randomly through our body and some of it just sort of ends up at an ion channel eventually, then wouldn't our thoughts and CNS activity in general be very chaotic and depend heavily on things like what we ate?

 

[Incunabula]

I like how you say "theorized"

I suffer badly from bruxism, be it from drugs, or just nightly, and calcium/magnesium supplements never made any difference for me.

 

[cannibalsnail]

This answer would take a LONG time to explain but at the core of it is entropy. Entropy is a universal law that dictates the universe tends towards chaos/disorder. This translates in chemistry terms to "molecules will always flow from regions of high concentration to regions of low concentration". By artificially controlling the levels of ions in different cells it can artificially induce a flow of charge.

Lets say (arbitrarily) that a neurone needs C++ ions inside of it to function. At a given moment in time the cell might have 100 C++ ions inside it. There are pumps along the plasma membrane (outside of the cell) called "Calcium ATPase" which utilise the energy from ATP to force C++ ions out of the cell against the concentration gradient. Because C++ cannot diffuse across the membrane naturally this lowers the concentration inside the cell and raises the concentration outside the cell. When a signal activates the cell it opens ion channels (proteins which permeate the entire membrane) which are exactly large enough to allow C++ ions to flow through but larger molecules won't. This causes the C++ to flow into the cell across the concentration gradient until the ion gate is locked again.

The exact role of Mg I am unclear on but I seem to recall it involving NMDA receptors. I think NMDA has an Mg lock on it, meaning that high levels of Mg cause a blockade of NMDA receptors, hence raising the amount of calcium excitation needed to activate a cell. This indirectly would translate to a heightened potential for muscle activation. But I am not 100% certain of the specifics and I could well be totally wrong.

 

[interleukin]

Like cannibalsnail said Mg is bound to the voltage gated NMDA receptor when the cell is below a certain potential. When the membrane potential reaches a certain level the Mg lock is released and the ion channel is open to Ca2+, Na+ etc. This will cause the neuron to fire an action potential among other things. NMDA receptors are pretty much everywhere in the brain. They have no special function in motor control as far as I know. Are NMDA antagonists considered muscle relaxants?
I will say this though - it works way better than anything I've tried including dopamine agonists for restless leg syndrome. I'm not sure if that has much to do with its mild NMDA antagonist action though. Maybe it is a cofactor for some enzymatic process involving dopamine or affects the dopaminergic system in some other indirect way.

 

[cannibalsnail]

I guess NMDA antagonists are a sort of muscle relaxant. Typical muscle relaxants act through GABA but anything which raises the activation potential for motor activity.

On the topic of restless leg syndrome, does anyone have any papers on the downstream effects of the D3 receptor? I'm curious why it raises the threshold for motor activity.

 

[SpunkySkunk347]

Thanks for the input guys, gave me a much clearer picture on ion channels.

And off topic, I've always sort of viewed restless leg syndrome as psychosomatic and just sort of silly.. I sometimes get the sensation in my legs like I'm compelled to move them, but I always just sort of told myself "Stop it. Don't think about it." and it goes away.. Do RLS sufferers have a much more persistent version of that or something?

 

[specialspack]

Here's a recent review of magnesium used in non-pharmacological muscle cramps - which says there's no real evidence so far:

http://www.ncbi.nlm.nih.gov/pubmed/22972143

I don't know what the proposed "theory" behind Mg being used to reduce bruxism or cramps due to stimulants is, but I would have thought it was about peripheral rather than CNS effects? If it was having significant CNS effects you'd probably expect it feel qualitatively different too.

 

[i are spectre]

i was under the impression that no one understands how magnesium even passes through the cell membrane.

ATP wraps around magnesium ions though, allowing certain cells to function properly. it is also present in DNA and from what i understand a ton of other stuff.

 

[SpunkySkunk347]

Here's a recent review of magnesium used in non-pharmacological muscle cramps - which says there's no real evidence so far:

http://www.ncbi.nlm.nih.gov/pubmed/22972143

I don't know what the proposed "theory" behind Mg being used to reduce bruxism or cramps due to stimulants is, but I would have thought it was about peripheral rather than CNS effects? If it was having significant CNS effects you'd probably expect it feel qualitatively different too.

I remember reading somewhere that amphetamine use resulted in elevated calcium levels and depleted magnesium levels.. I also remember someone saying that 'chelated' magnesium had a higher bioavailability than run-of-the-mill multivitamin quality magnesium, although I don't even know what "chelated" means really (something to do with how magnesium binds to other atoms) so I don't know how accurate that is

It sounded convincing back then, but having bought magnesium supplements since then and seeing how they affected my amphetamine tolerance, I'm not convinced that it did anything more than a placebo effect.
Sometimes on amphetamine, all it takes to reduce physical side effects is for a user to remind themselves to momentarily get up and stretch, drink water, etc.. It can't be healthy to sit in one spot doing the same thing for hours upon hours. And on the contrary, you can't constantly be up and moving on amphetamine either or you'll burn yourself out. Amphetamine use seems like one great big balancing act a lot of the time.. yet mathematicians and scientists have used it regularly with success (then again, I recall reading that Hitler was a meth user).. there is also of course the broken medical community which seems to insist that amphetamine use has a legitimate medical use for under-motivated adolescents. I just don't know.

 

[Jakeperson]

Here's a recent review of magnesium used in non-pharmacological muscle cramps - which says there's no real evidence so far:

http://www.ncbi.nlm.nih.gov/pubmed/22972143

I don't know what the proposed "theory" behind Mg being used to reduce bruxism or cramps due to stimulants is, but I would have thought it was about peripheral rather than CNS effects? If it was having significant CNS effects you'd probably expect it feel qualitatively different too.

As a methamphetamine addict, I can feel the difference.

 

[SpunkySkunk347]

As a methamphetamine addict, I can feel the difference.

I've never done methamphetamine, just amphetamine. I can't even begin to fathom a dose of speed hitting me all at once from smoking/snorting/shooting it like a meth user does.. it would probably terrify me and confuse me.. There have been times from just swallowing regular amphetamine where I had extended debates with myself whether or not I needed to go to the psyche ward; I can't even imagine what abusing meth is like, its probably hell on earth..
What's the difference that you notice though? Your drug use being just a "nightmare" as opposed to "eternal damnation"?
I guess my point is, why are you doing it?
Sorry, I know this is advanced drug discussion, I am not trying to instigate any sort of drama whatsoever.

 

[specialspack]

As a methamphetamine addict, I can feel the difference.

Oh, well that's that decided then... 8(

What's the difference that you notice though? Your drug use being just a "nightmare" as opposed to "eternal damnation"?
I guess my point is, why are you doing it?

Er... because many people find methamphetamine one of the most euphoric drugs they've ever tried? If you considered going to hopsital off a single dose of oral d-amp, it must have been a pretty massive dose. Or your psyche isn't up to dealing with stimulants, and you should probably not do them.

On topic - http://en.wikipedia.org/wiki/Chelation

 

[SpunkySkunk347]

Er... because many people find methamphetamine one of the most euphoric drugs they've ever tried? If you considered going to hopsital off a single dose of oral d-amp, it must have been a pretty massive dose. Or your psyche isn't up to dealing with stimulants, and you should probably not do them.

It was a week long binge without sleep, and I accidentally drank a tea with St John's Wort in it which I believe threw me into a psychosis

 

[sekio]

When you're on a week long bender of any sort, psychosis can be precipitated by almost anything.

 

[DJHENRU]

I think chelated means that less is kept Endocrinol system(like heavy metals) when taken in toxic amounts.

 

[SpunkySkunk347]

From what I understand now after reading a bit (and I don't know the technical way of wording this), chelated magnesium is magnesium paired with an amino acid for better absorption out of the digestive tract, the amino acid 'protects' the magnesium from "being complexed by insoluble salts within the stomach" (from the wikipedia article on chelation) -- so basically, if I get this right, when non-chelated magnesium is ingested, the majority of it is useless and passes right on through the digestive tract never being utilized?

It makes me wonder if the magnesium that is naturally present in foods (such as brocolli) is somehow 'naturally chelated' or protected in some way for better absorption.. I remember hearing years and years ago that most multi-vitamin supplements aren't as useful as we think they are, because some of the vitamins and minerals are only utilized effectively by our body in the presence of the other nutrients they are normally found with (i.e., food).

I don't think our digestive tract ever evolved to just be able to pull a day's load of raw vitamins/minerals out of nothing but a glass of water.

 

[sekio]

All 'chelated' means is there is some organic molecule that 'wraps around' the magnesium. Normally 'free' magnesium ions attract a 'shell' of water molecules, or react with certain acids that reduce the ability of the cation to eb absorbed by biological systems, and hence are less well absorbed than e.g. sodium. Also it will react with bile acids to form a hard precipitate.
Chelation does not have to be by amino acid, for instance citrate is an excellent chelator, as is EDTA.

Normally plants and animals do not contain very much 'free' magnesium, it is almost always present in a water-soluble form, as a salt or as a chelate.

Even if you eat raw magnesium oxide ('magnesia'), portions of it are converted to the water-soluble magnesium hydroxide and magnesium chloride in your stomach, and absorbed. Just not very well, 10% or less BA.

 

[red_bandit]

supposed cause of magnesium muscle relaxant properties; action potential generation

The purported muscle relaxant properties of Magnesium primarily come from its effect directly on muscle tissue contraction and not the nerves that stimulate them. When a motor neuron (a nerve cell that innervates a muscle) is activated, it releases the neurotransmitter acetylcholine (ACh) into the neuromuscular junction (NMJ; the synapse between the motor neuron and the muscle) and activates receptors on the surface of the muscle cells. This leads to the opening of Calcium channels. The increase in calcium concentrations inside the muscle cells activates the tiny motor proteins that lead to shortening of the individual muscle cells and contraction of entire muscle.

The key is the rush of calcium ions into the muscle cell in response to motor neuron activity. Magnesium competes with calcium to enter the cells through these channels. BUT...it can't signal the contraction like calcium does. The greater the Mg++/Ca++ ratio, the less effective the electrical signals from the motor neuron are going to be at contracting the muscle.

What you guys have mentioned about NMDA receptor blockade by Mg++ is absolutely correct but that process is thought to have very little to do with Mg++ muscle relaxation.

One final thing to clarify: OP mentioned action potentials and what ions/channels are involved there. The VAST majority of action potentials are the result of sodium moving into the neuron and potassium moving out via voltage-gated channels that are specific for either one of those ions. Calcium is sometimes used to generate action potentials, but it's very rare compared to sodium action potentials.

I know I glossed over a lot of details. Please feel free to PM me if you have questions or want some references. This is kind of my thing since I specialize in using sensitive electrodes to record the tiny electrical signals between neurons

/super-nerd