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Ions may determine sleep and wakefulness

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Praxis.

Praxis.

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This is older news but I thought it was pretty cool! 8)

How do we switch from sleep to arousal and back? Ding et al. found that a combination of modulatory neurotransmitters influenced the levels of extracellular ions in the brain (see the Perspective by Landolt and Holst). This influence was not driven by changes in local neuronal firing, suggesting direct effects of the neuromodulators on extracellular ion composition. However, these changes in interstitial ion levels could switch a brain from wakefulness to sleep. Changes in extracellular ions may thus be a cause, rather than a consequence, of sleep/wake-dependent changes in neuronal activity.

Abstract
Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K+ concentration ([K+]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor–independent elevations of [K+]e concomitant with decreases in [Ca2+]e, [Mg2+]e, [H+]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K+]e while increasing [Ca2+]e, [Mg2+]e, and [H+]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.
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In plain english: Changes in ion concentrations, not nerve cell activity (as previously believed), may be responsible for waking/dream states.

Check out the full study...

And here's an excerpt from a sciencenews article that summarizes the results of the study pretty concisely:

In the study, Nedergaard’s group administered a “wake cocktail” of neuromodulator chemicals to mouse brains. Levels of potassium ions floating between brain cells increased rapidly after the treatment, the researchers found. That ion change happened even when the researchers added tetrodotoxin to stop neuron activity. The results suggest that the brain chemicals — norepinephrine, acetylcholine, dopamine, orexin and histamine — directly affect ion levels with no help from neurons. Exactly how the chemicals manage ion levels still isn’t known.

Similar changes happen under anesthesia. When awake mice were anesthetized, potassium ion levels in their brains dropped sharply, while levels of calcium and magnesium rose, the researchers found. As mice awoke from anesthesia, potassium ion levels rose quickly. But calcium and magnesium levels took longer to drop. As a result, the mice “are totally confused,” says Nedergaard. “They bump into their cages, they run around and they don’t know what they are doing.”

Those results may help explain why people are groggy after waking up from anesthesia; their ion levels haven’t returned to “awake” levels yet, says Amita Sehgal, a sleep researcher at the University of Pennsylvania School of Medicine.

Learning more about how ions affect wake and sleep may eventually lead to a better understanding of sleep, consciousness and coma, Nedergaard says.

Full article...
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This is very interesting, I wonder if there are any good ways to modulate the concentrations of ions in the extracellular fluid via diet.
 
Psybin said:
This is very interesting, I wonder if there are any good ways to modulate the concentrations of ions in the extracellular fluid via diet.
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Good question. This is all pretty far beyond my current understanding of biochemistry so I'm not sure if it's even relevant, but this is what I was able to find.

ions modulate everything in neurological functions. polarization/depolarization.
in plain english, changes in ion concentrations = nerve cell activity.
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This might be a silly question--but if this was already generalizable then why the need for this study? What did it prove if we already knew that ions control neural activity?
 
benzyme said:
ions modulate everything in neurological functions. polarization/depolarization.
in plain english, changes in ion concentrations = nerve cell activity.

tetrodotoxin is a classic inhibitor of the SNARES protein complex, blocks the Na+ ion channel.
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This a bit of an oversimplification, much like saying that votes and a president are the same thing because one is precipitated by the other. While nerve cell activity might depend on electrical potential which depends on ion concentrations, the two are not equivalent. In the same way, a picture of your dog is not a pixel, nor the other way around.

In any case, I think the main point of the study is that the specific nerve impulses themselves, while a result of ion concentrations, are not inherently responsible for whether one is in the waking or sleep state, while the concentrations of K+ and Ca2+ and Mg2+ respectively appear to be directly responsible for the distinction.

My apologies if misinterpreted your post.
 
Praxis. said:
Psybin said:
This is very interesting, I wonder if there are any good ways to modulate the concentrations of ions in the extracellular fluid via diet.
Click to expand...
Good question. This is all pretty far beyond my current understanding of biochemistry so I'm not sure if it's even relevant, but this is what I was able to find.

ions modulate everything in neurological functions. polarization/depolarization.
in plain english, changes in ion concentrations = nerve cell activity.
Click to expand...
This might be a silly question--but if this was already generalizable then why the need for this study? What did it prove if we already knew that ions control neural activity?
Click to expand...

they are seeking to show how it occurs, how it affects sleep and waking cycles. for every question that gets answered, another 20 pop up.
 
benzyme said:
perhaps I should've been more clear. neural activity, or lack thereof, directly correlates to action potential. that is not oversimplification at all, rather, it is simple cause and effect.
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EDIT: Yes, action potential and neural activity are nearly synonymous, but we're talking about concentration of ions, which has a broader effect than just action potential, which is why this is such an interesting discovery, at least in my opinion.
 
what did you think creates action potential?
ligands..and threshold values are measured in mM, uM, nM, etc.
ligands can be anything from small molecules to, well, ions.
nothing new there.

what this study seems to seek is the correlation between the cause/effect aspect of those concentrations to states of sleep/wakefulness.

there results suggest that the brain chemicals — norepinephrine, acetylcholine, dopamine, orexin and histamine — directly affect ion levels with no help from neurons. Exactly how the chemicals manage ion levels still isn’t known
Click to expand...

that is, IMO, fairly interesting...the chicken before the egg, so to speak
 
benzyme said:
what did you think creates action potential?
ligands..and threshold values are measured in mM, uM, nM, etc.
ligands can be anything from small molecules to, well, ions.
nothing new there.

what this study seems to seek is the correlation between the cause/effect aspect of those concentrations to states of sleep/wakefulness.

there results suggest that the brain chemicals — norepinephrine, acetylcholine, dopamine, orexin and histamine — directly affect ion levels with no help from neurons. Exactly how the chemicals manage ion levels still isn’t known
Click to expand...

that is, IMO, fairly interesting...the chicken before the egg, so to speak
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Right, I agreed. I don't really get what you're trying to assert. I have a degree in biochemistry so you don't need to try and dumb it down. The extracellular conc. of ions contributes to action potential and thus neural activity, yes, I get that. But there's more to it than that, hence the experimental results. The conc. of K+ for example has other biological effects other than contributing to an action potential, or perhaps it acts as a ligand at a site we don't yet know of or understand completely which has a downstream effect that is counter=intuitive?

At any rate, it would appear neither of us are adding anything unique or groundbreaking, so maybe we should agree to disagree and let the thread do it's thing.

EDIT: The ion conc. is the big picture, but it doesn't determine what each neuron does - that's what the conc. of ions INSIDE the cell does, with respect to the extracellular conc. If the extracellular conc. drops globally, that has a widespread effect on neural activity very different from changes in local neural activity, which is what is potentially exciting.
 
benzyme said:
actually, I don't even think we are disputing anything, probably just miscommunication.
the effect of secondary messengers on ion concentrations is what I find curious.
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Well I've been meaning to get some sleep for a long while now, so you're probably right. My apologies.
 
Praxis. said:
This is older news but I thought it was pretty cool! 8)

Yes, very cool! I remember seeing it recently and being fascinated by the fact that DMT affects the Sigma-1 receptors which in turn inhibit voltage gated sodium ion channels and also affects Ca2+ and K+ channels... a possible link to the often supposed idea that DMT is elevated in sleep and dream states?

I am sure it is all much more complicated than that, and any DMT release would seem to be happening later in the night anyway, but it just felt like there could be some relationship going on there.

In general I am fascinated by sleep and dreams, just wish I had majored in biochem or organic chemistry to better understand it all!
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