Heavy metal, receptor blockage?

[DevilSolution]

It is true that heavy metals have a 15 year half life in neurological cells? And do they block receptors from receiving transmitter loads? And can you purge the metals??

 

 

Regards.

[Ringer]

http://www.psr.org/environment-and-health/confronting-toxics/heavy-metals/

[DevilSolution]

How do you flush them??

[CharonY]

Heavy metals are removed from the body naturally, but at a slow rate. The results are the half-lives of years (in terms of persistence and not to be confused with half-life in terms of stability). For these reasons heavy metals can bioaccumulate (i.e. if you take in more than your body can remove in that time frame). There are generally no specific ways to accelerate that, though there are measure for acute high-level toxic intakes (mostly trying to get it out of your gut before more gets absorbed.. Once the metals get into your tissue, there is fairly little that can be done knowledge.

The way they cause harm are, as mentioned above, manifold and there is not a specific target of toxic effects.

Edited December 6, 2013 by CharonY

[DevilSolution]

Heavy metals are removed from the body naturally, but at a slow rate. The results are the half-lives of years (in terms of persistence and not to be confused with half-life in terms of stability). For these reasons heavy metals can bioaccumulate (i.e. if you take in more than your body can remove in that time frame). There are generally no specific ways to accelerate that, though there are measure for acute high-level toxic intakes (mostly trying to get it out of your gut before more gets absorbed.. Once the metals get into your tissue, there is fairly little that can be done knowledge.

The way they cause harm are, as mentioned above, manifold and there is not a specific target of toxic effects.

 

So they can block neuron receptors? Or some particular aspect of the cell like mitochondria??

 

IS this also part of the reason lead and mercury are poisonous?

Edited December 7, 2013 by DevilSolution

[CharonY]

As I said, the actions are very diverse, they may interfere with the action of certain proteins, cause oxidative stress etc. In some cases the actions may be direct or in others indirect. It is not trivially to locate where the metals actually interact with in vivo. E.g. you could just throw a protein and a metal together and figure out whether they associate closely but that tell you little about the actions in the body.

 

For example in rats lead studies have shown altered binding of NMDA receptors to their cognate targets. For some it decreases binding, in others it increases. More likely targets for heavy metal binding are enzymes that normally interact with similar ions (i.e. where the binding site may actually be similar to a heavy metal ion). In cases for Pb 2+ this may include divalent ion channels (such as for Ca2+). If you are thinking in terms of receptors for neurotransmitters I think the affinity would be rather low and would require concentrations at which far worse damage would already be done.

[DevilSolution]

If you are thinking in terms of receptors for neurotransmitters I think the affinity would be rather low and would require concentrations at which far worse damage would already be done.

 

Yeh quite specifically that, what about long term build up? How well does it cross the blood brain barrier? And does it enter through atmosphere or specific chemical ingestion / biosythn?

[CharonY]

Bioaccumulation is just another term for long-term build up in a biological context. Continuous exposure will lead to increased values in tissues. Most metals should pass the brain-blood barrier with similar efficiency as most other cations (I know of studies with lead and iron, less certain about detailed values for others). Heavy meal exposure can take different forms and depends highly on the metal.

Outside occupational or catastrophic exposures ingestion is probable the most common route.

[DevilSolution]

So we can hypothetically have metals sitting in our neurons right now? Or is there actually definitely gona be??

[Ringer]

IIRC there are heavy metals in cells, but not enough for toxicity to be a problem.

[CharonY]

We all have certain heavy metals, some of which, as e.g. copper and iron are absolutely essential for our survival. Pretty much everyone will have some level of other heavy metal contamination. But as usual, as long as the concentration does not reach harmful levels we will never notice.

[CPG]

As an aside from the OP's reference to synaptic communication, certain heavy metal ions (I'm thinking particularly of divalent cations here) may alter the intrinsic excitability of individual neurons of interest due to their molecular interactions with voltage-gated ion channels. For example, I regularly use cadmium because in the neural networks I study, it physically occludes the pores of the calcium channels present and effectively takes Calcium currents out of the equation. It's useful to do this kind of manipulation in experimental electrophysiology because you can then measure other membrane currents without the contamination of calcium flux and its effects. I just wanted to add the important bit about effects on non-synaptic neuronal intrinsic properties because it seemed that only chemical synaptic ionotropic receptors were really being considered thus far, which would ignore how individual neurons process whatever inputs they do receive.

 

I'm afraid I can't speak very knowledgeably to human health consequences, concentration-dependent effects, half-life in vivo, or other concerns in the OP. However, I do agree with what is said above about the complexity you're likely to deal with at that level and the general promiscuity of biomolecular interactions. Just adding another potential neuronal effect to the list.

[DevilSolution]

For example, I regularly use cadmium because in the neural networks I study, it physically occludes the pores of the calcium channels present and effectively takes Calcium currents out of the equation. It's useful to do this kind of manipulation in experimental electrophysiology because you can then measure other membrane currents without the contamination of calcium flux and its effects.

 

What neurological effect does this have? I dont fully understand all the terminology, mainly the "it physically occludes the pores of the calcium channels present and effectively takes Calcium currents out of the equation" part.

 

Regards.

[CPG]

 

What neurological effect does this have? I dont fully understand all the terminology, mainly the "it physically occludes the pores of the calcium channels present and effectively takes Calcium currents out of the equation" part.

 

Regards.

 

Calcium would normally be able to flow across the cell membrane through protein complexes that form calcium channels. Physically occluding the pores essentially means Cd2+ gets stuck in these structures and thus prevents calcium from flowing through the channels. If calcium cannot flow, then any voltage changes that would result from calcium currents will not happen, and many other intracellular processes dependent upon calcium influx will not happen. The list of things intracellular Ca2+ does would be a very long one.

 

By "taking calcium currents out of the equation" I just mean that it can help achieve cleaner results in experimental electrophysiology. There are actual equations for this stuff, but that's typically when the eyes begin to glaze over so instead, to illustrate...

 

Let's say I am interested in a particular potassium current, and I want to characterize the role of electrical current flowing across a cell membrane that is due to voltage-gated potassium channels. It would be very helpful, then, to block any other possible sources of current aside from the potassium current I care about. In order to do that I might add cadmium to the solution around the cell to block Ca2+ channels, and then I add other substances to block sodium channels and any other path for charged particles to move across the membrane except those potassium channels that I care about. Then if I measure current flow across that cell membrane, I can be confident it is the one I wanted to characterize and the properties of that current are not contaminated by calcium currents or other currents.

 

http://en.wikipedia.org/wiki/File:1K4C.png

 

 

A visual aid from wikipedia to help in thinking about ions moving across a channel, and how the molecular properties of ion channels provide their selectivity. This is a potassium channel illustrated here (chosen because their structure & function is particularly well understood), so you'd find a slightly different structure providing the selectivity in a Ca2+ channel. These "selectivity filters" in ion channels tend to be highly conserved and are targets for many toxins, poisons, etc.

 

In this case, I was referring to Cd2+ being similar enough to Ca2+ to get into the pore / selectivity filter, but different enough that it can't pass through and instead it remains in the pore and prevents Ca2+ from passing through.

Edited January 10, 2014 by CPG