3 ms·

The action potential is an electrical manipulation of reversible abrupt phase changes in the lipid bilayer. Normally the lipid bilayer is in a liquid phase but

The action potential is an electrical manipulation of reversible abrupt phase changes in the lipid bilayer. Normally the lipid bilayer is in a liquid phase but the the switching out of monovalent sodium for bivalent calcium ions changes the number of phospholipid carboxyl head groups each ion is electrostatically associated with. This changes the heat capacity and causes the lipid membrane to become a solid/gel phase. The action potential itself is the propagation of this solid phase. This is how thermodynamics can effect neurons. And this is why dissolving gases into the lipid membrane, like nitrogen in the article, cause change the thermodynamic properties like the heat capacity and retard the solid phase a bit. Light gases increase liquidity. That's the anesthetic effect that reduces firing rates. And that's why local atmospheric pressure matters in gas anesthesia dosing. It's not that the old hogkin-huxley purely electrical circuit model is "wrong", it's a fine approximation of some effects. But it certainly can't explain the reversible uptake and release of heat during a passing action potential, nor the changes in birefringence and optical scattering, nor why nitrogen can act as an anesthetic like in this case.

Robelius 3y ago
Are you saying that what's happening is the permeability of the cell membrane changes with their physical states (from a scale of "more liquid" to "more solid")and that change impacts the transmission rate of the neurons? And an example of this would be an anesthesiologist putting you under is them making your cell membrane more solid to increase the resistance those neuron transmissions experience, just like adding more resistance to a circuit to reduce the voltage? Disclaimer that biological sciences aren't my strength so I'm just trying to understand what you're saying.
- superkuh 3y ago
  No, it's not about ions going through the membrane or membrane pemeability. It is not about resistance to ions flow across the 10nm they travel perpendicular to the membrane. Transport of ions across through ion channels are required for the effect but the membrane itself (usually) is not leaking and I'm not talking about changes in leakage. It is about how the various ions like Na+ and Ca+2 associated with the membrane itself to change the membrane's physical properties. When there's lots of light gas anesthetic dissolved in the lipid membrane keeping the heat capacity low (disordered) it is thermodynamically harder (requires more energy) to form the organized 'solid' (actually more like a gel) state that propagates as the action potential. ref: https://arxiv.org/abs/1805.11481 https://arxiv.org/abs/1805.11481 - good overview paper, http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Membrane/ http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Mem... - other papers/books on the subject.
tiffanyg 3y ago
Mm-hmm, Mm-hmm... Oh! Oh, yeah... mm, mm. Mmm! I know some of these words!* More seriously - thanks for that description! It's always interesting to see just how many "principles" &/ "laws" etc. (our compartmentalized / simplified models) underlie certain kinds of physical behavior (and, sort of, emergent properties thereof). Even just sticking together enough of the simplest models can be kind of surprising and not so easy to reason about / handle with much "facility". I've never learned much about anesthesia, and the little bits I have learned, here and there - and usually only in very specific contexts, makes it so most of this info doesn't really stick in my head. So, I appreciate getting a bit of refresher / learning every now and again. Particularly, in how it ties together with everything else involved. Thanks! * https://youtu.be/sl2W85KKzgc https://youtu.be/sl2W85KKzgc
topaz0 3y ago
Worth noting that, while this model has been around for a few decades, it does not have many adherents among neuroscientists. Which is not to say that it is wrong necessarily, just that I wouldn't want readers to get the wrong idea that this is a consensus view.
- genewitch 3y ago
  neuroscientists are just mad that "gut feeling" is actually the truth, and we're generally being manipulated by the billions of microbes in our guts. Simple example: why do people crave cake when they're on a diet that doesn't allow cake? There are microbes that convert stuff in grasses (corn, etc) into opioids. Opioids are great, make us feel great, and if we are used to having opioids and suddenly stop, we go into opioid withdrawal. I haven't really put a fine point on the grand theory of gut-mind-body interaction, but i'm fairly certain that nearly every disorder or disease that isn't external (like radiation or malaria) will eventually be traced back to gut flora, from auto-immune disorders to depression.
  - gamblor956 3y ago
    Cake does not generally contain grasses...and if it were true that there were trains of gut flora that converted sugars to opioids almost everyone in America would live in a perpetual state of intoxication. Sugar withdrawal is also not even remotely similar to opioid withdrawal.
    - Filligree 3y ago
      Cake usually contains flour, which is made from wheat, which is a form of grass...
      - gamblor956 3y ago
        No, wheat is made from the seeds, i.e., the grain, of wheatgrass, not the grass. That some bacteria are able to eat the cellulose or other cells in grass is absolutely unrelated to their ability to consume the completely different structures and nutrients in a seed.
killjoywashere 3y ago
Yeah, physician (pathologist, specifcally) with a degree in physics here. I'm going through articles in other tabs right now just because I'm skeptical enough to consider crazy ideas (always good to build bulwarks), this is, at best hypothetical, but mainly the chain of causality in the above statements is a hot mess. I spend a lot of time looking at cell membranes. More than almost all of humanity. The naive Fluid Mosaic Model is certainly incomplete, but let's let Dr. Nicholson himself (the author of the original description) have a chance to provide his update first (1). So, yes, there's lot of other stuff going on, but certainly the basic organizing concepts are intact. I'll allow the idea that the transfer of ions across the membrane is a thermodynamic effect. Of course it is. The whole nitrogen vs helium thing works well enough in my mind with just "thermodynamics". Yeah, sure. But this statement "The action potential itself is the propagation of this solid phase" does not pass the sniff test for me. The action potential is a self-propagating electric field tripping channels along the way, propagating along inner and outer surfaces of the membrane, the channels are what make it self-propagating. Nothing about the concept of "solid" makes sense at these scales in a biological system. Everything is just more or less bound, and that neighbor-to-neighbor binding is entirely secondary to the mammoth electrical field whipping down the axon. (1) Nicholson GL, de Mattos GF. A Brief Introduction to Some Aspects of the Fluid–Mosaic Model of Cell Membrane Structure and Its Importance in Membrane Lipid Replacement. 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708848/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708848/
- superkuh 3y ago
  Yes, this is a contested theory, but it's not a crackpot theory. I'm well aware of the fluid mosaic model. It is not mutually exclusive with what I've described, in fact it's the base from which this theory is formed. And it is not my theory, but the theory first formulated by literally the guy that discovered the mechanism of action of myelinated action potentials (Ichiji Tasaki, who worked on it during his entire time at the NIH). Call it crackpot if you want but please don't do so just because you've misinterpreted a a short forum post trying to introduce a complex concept in a concise way. To clear it up for you, the transfer of ions across the membrane by ion channels is not something I'm debating. Nor am I saying that the electrical field isn't required for the action potential to propagate. If you took that away from my post I can understand you thinking it's crackpottery. I'm just saying it's not the whole picture. When there's lots of light gas anesthetic dissolved in the lipid membrane keeping the heat capacity low (disordered) it is thermodynamically harder (requires more energy) to form the organized 'solid' (actually more like a gel to be pedantic) state that propagates with/as the action potential. All these things are happening together, and more (like, how the lateral pressure profile might link the lipid state to ion channel conformational changes, etc). Simple electrical models cannot explain reversible uptake and release of heat (resistance cannot do this) with the passing of the action potential. Nor the reason atmospheric pressure changes dosage, nor the reason there's a change in optical birefringence and scattering. So you know what it describes is not the full picture. But don't take my word for it, go read Tasaki or Heimburg's work on this if you want to understand the detail. http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Membrane/ http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Mem...

Robelius 3y ago

Are you saying that what's happening is the permeability of the cell membrane changes with their physical states (from a scale of "more liquid" to "more solid")and that change impacts the transmission rate of the neurons? And an example of this would be an anesthesiologist putting you under is them making your cell membrane more solid to increase the resistance those neuron transmissions experience, just like adding more resistance to a circuit to reduce the voltage? Disclaimer that biological sciences aren't my strength so I'm just trying to understand what you're saying.

superkuh 3y ago
No, it's not about ions going through the membrane or membrane pemeability. It is not about resistance to ions flow across the 10nm they travel perpendicular to the membrane. Transport of ions across through ion channels are required for the effect but the membrane itself (usually) is not leaking and I'm not talking about changes in leakage. It is about how the various ions like Na+ and Ca+2 associated with the membrane itself to change the membrane's physical properties. When there's lots of light gas anesthetic dissolved in the lipid membrane keeping the heat capacity low (disordered) it is thermodynamically harder (requires more energy) to form the organized 'solid' (actually more like a gel) state that propagates as the action potential. ref: https://arxiv.org/abs/1805.11481 https://arxiv.org/abs/1805.11481 - good overview paper, http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Membrane/ http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Mem... - other papers/books on the subject.

tiffanyg 3y ago

Mm-hmm, Mm-hmm... Oh! Oh, yeah... mm, mm. Mmm! I know some of these words!* More seriously - thanks for that description! It's always interesting to see just how many "principles" &/ "laws" etc. (our compartmentalized / simplified models) underlie certain kinds of physical behavior (and, sort of, emergent properties thereof). Even just sticking together enough of the simplest models can be kind of surprising and not so easy to reason about / handle with much "facility". I've never learned much about anesthesia, and the little bits I have learned, here and there - and usually only in very specific contexts, makes it so most of this info doesn't really stick in my head. So, I appreciate getting a bit of refresher / learning every now and again. Particularly, in how it ties together with everything else involved. Thanks! * https://youtu.be/sl2W85KKzgc https://youtu.be/sl2W85KKzgc

topaz0 3y ago

Worth noting that, while this model has been around for a few decades, it does not have many adherents among neuroscientists. Which is not to say that it is wrong necessarily, just that I wouldn't want readers to get the wrong idea that this is a consensus view.

genewitch 3y ago
neuroscientists are just mad that "gut feeling" is actually the truth, and we're generally being manipulated by the billions of microbes in our guts. Simple example: why do people crave cake when they're on a diet that doesn't allow cake? There are microbes that convert stuff in grasses (corn, etc) into opioids. Opioids are great, make us feel great, and if we are used to having opioids and suddenly stop, we go into opioid withdrawal. I haven't really put a fine point on the grand theory of gut-mind-body interaction, but i'm fairly certain that nearly every disorder or disease that isn't external (like radiation or malaria) will eventually be traced back to gut flora, from auto-immune disorders to depression.
- gamblor956 3y ago
  Cake does not generally contain grasses...and if it were true that there were trains of gut flora that converted sugars to opioids almost everyone in America would live in a perpetual state of intoxication. Sugar withdrawal is also not even remotely similar to opioid withdrawal.
  - Filligree 3y ago
    Cake usually contains flour, which is made from wheat, which is a form of grass...
    - gamblor956 3y ago
      No, wheat is made from the seeds, i.e., the grain, of wheatgrass, not the grass. That some bacteria are able to eat the cellulose or other cells in grass is absolutely unrelated to their ability to consume the completely different structures and nutrients in a seed.

killjoywashere 3y ago

Yeah, physician (pathologist, specifcally) with a degree in physics here. I'm going through articles in other tabs right now just because I'm skeptical enough to consider crazy ideas (always good to build bulwarks), this is, at best hypothetical, but mainly the chain of causality in the above statements is a hot mess. I spend a lot of time looking at cell membranes. More than almost all of humanity. The naive Fluid Mosaic Model is certainly incomplete, but let's let Dr. Nicholson himself (the author of the original description) have a chance to provide his update first (1). So, yes, there's lot of other stuff going on, but certainly the basic organizing concepts are intact. I'll allow the idea that the transfer of ions across the membrane is a thermodynamic effect. Of course it is. The whole nitrogen vs helium thing works well enough in my mind with just "thermodynamics". Yeah, sure. But this statement "The action potential itself is the propagation of this solid phase" does not pass the sniff test for me. The action potential is a self-propagating electric field tripping channels along the way, propagating along inner and outer surfaces of the membrane, the channels are what make it self-propagating. Nothing about the concept of "solid" makes sense at these scales in a biological system. Everything is just more or less bound, and that neighbor-to-neighbor binding is entirely secondary to the mammoth electrical field whipping down the axon. (1) Nicholson GL, de Mattos GF. A Brief Introduction to Some Aspects of the Fluid–Mosaic Model of Cell Membrane Structure and Its Importance in Membrane Lipid Replacement. 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708848/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708848/

superkuh 3y ago
Yes, this is a contested theory, but it's not a crackpot theory. I'm well aware of the fluid mosaic model. It is not mutually exclusive with what I've described, in fact it's the base from which this theory is formed. And it is not my theory, but the theory first formulated by literally the guy that discovered the mechanism of action of myelinated action potentials (Ichiji Tasaki, who worked on it during his entire time at the NIH). Call it crackpot if you want but please don't do so just because you've misinterpreted a a short forum post trying to introduce a complex concept in a concise way. To clear it up for you, the transfer of ions across the membrane by ion channels is not something I'm debating. Nor am I saying that the electrical field isn't required for the action potential to propagate. If you took that away from my post I can understand you thinking it's crackpottery. I'm just saying it's not the whole picture. When there's lots of light gas anesthetic dissolved in the lipid membrane keeping the heat capacity low (disordered) it is thermodynamically harder (requires more energy) to form the organized 'solid' (actually more like a gel to be pedantic) state that propagates with/as the action potential. All these things are happening together, and more (like, how the lateral pressure profile might link the lipid state to ion channel conformational changes, etc). Simple electrical models cannot explain reversible uptake and release of heat (resistance cannot do this) with the passing of the action potential. Nor the reason atmospheric pressure changes dosage, nor the reason there's a change in optical birefringence and scattering. So you know what it describes is not the full picture. But don't take my word for it, go read Tasaki or Heimburg's work on this if you want to understand the detail. http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Membrane/ http://erewhon.superkuh.com/library/Neuroscience/Lipid%20Mem...