What neutralizes important ions in the cell?

[Erland]

I am very interested in biochemistry, and in particular the metabolism of the cell. Important molecules for cell metabolism are ATP (and ADP) and NAD+ (and NADH). ATP, ADP and NAD+ are ions: ATP and ADP have negative charge (as have the free phosphate ions) and NAD+ has positive charge. But the cell as a whole is neutral (at least I think so, and in any case, all the cells in an organism has no significant total charge). Therefore, threre must exist other ions (or perhaps free electrons) in the cell which neutralize these ions. Which are these ions?
Which positive ions neutralize ATP, ADP and free phospate ions? Which negative ions (or is it free electrons) neutralize NAD+?

 

[Simon Bridge]

An object may be electrically neutral, and contain charges, provided there are about the same number of positive and negative charges. The individual ions need not be "neutralized" in any specific way.

A biological cell is an active structure and will typically have many different ions in it at any time - not just the "important" ones - and it need not be electrically neutral all the time either.

Do you have any specific reason to suspect that living cells are electrically neutral or is that a guess?

 

[Erland]

Do you have any specific reason to suspect that living cells are electrically neutral or is that a guess?

If cells were typically electrically charged, they would attract and/or repel each other, and that is not what we typically see...

 

[Pythagorean]

What about neurons? Neurons are held at relatively low voltage potential compared to the extracellular space, but we don't see neurons repelling each other. Perhaps the force of electrodynamical forces are not enough compared to the connective tissues in the extracellular matrix.

In fact, even non-neuronal cells have some kind of currents flowing in and out of them for signaling:

Transmembrane voltage potential controls embryonic eye patterning in Xenopus laevis.
http://www.ncbi.nlm.nih.gov/pubmed/22159581

 

[Erland]

That current flows through a cell doesn't mean that it has a charge, as long as equally much charge flows into the cell as out from it. And although it may happen that some neighboring cells may be charged (but not very big charges, I think) an organism as a whole is rarely charged (exceptions may perhaps exist, such as electric eels). I am certain that my own total charge is negligible.

 

[DiracPool]

But the cell as a whole is neutral (at least I think so, and in any case, all the cells in an organism has no significant total charge). Therefore, threre must exist other ions (or perhaps free electrons) in the cell which neutralize these ions. Which are these ions?
Which positive ions neutralize ATP, ADP and free phospate ions? Which negative ions (or is it free electrons) neutralize NAD+?

Hi Erland, you're kind of missing the whole point of what cellular respiration/metabolism is. Cells do "work" like replication, protein synthesis, signal transmission, etc. by keeping their electrochemical states far from equilibrium. Work is done as the natural state of the system then tries to achieve equilibrium. Looking at it from an attractor-dynamics perspective in colloquial terms, the cell works to continually try to push a ball artificially up the side of a bowl, while the natural forces on the ball are always trying working to settle the ball at the bottom of the bowl. As the ball falls down the side of the bowl toward the bottom, work is done, e.g., the execution of a neuronal action potential or when ATP is hydrolyzed into ADP in order to produce energy for cellular respiration.

If, at that point, the cell would then let these processes go to equilibrium, which would amount to your comment about the cell as a whole being neutral, the cell would simply die and that would be that. In order to prevent this, the cell engages in respiratory cycles such as the Krebs (aka, citric acid and TCA) cycle in animals, and the Calvin cycle in plants. The action of these cycles reflects the cell trying to push the ball up the side of the bowl as it moves more toward equilibrium, these are the cycles that generate ATP and that maintain a non-zero potential voltage across the neuronal membrane through membrane ion pumps:

From: http://en.wikipedia.org/wiki/Citric_acid_cycle

Two carbon atoms are oxidized to CO2, the energy from these reactions being transferred to other metabolic processes by GTP (or ATP), and as electrons in NADH and QH2. The NADH generated in the TCA cycle may later donate its electrons in oxidative phosphorylation to drive ATP synthesis

You may also want to review this article which talks about how cognitive processes and perceptual recognition works by maintaining electrochemical states in the brain far from equilibrium. http://www.ncbi.nlm.nih.gov/pubmed/?term=freeman,+far+from+equilibrium

Finally, I would recommend picking up Becker's book, The world of the cell. This is a great book, one of the ones we used in my molecular biology class as an undergrad. https://www.amazon.com/dp/0321689631/?tag=pfamazon01-20

Damn, it's in its 8th edition now. I think I have the third edition, eegads, time goes fast

 

[Pythagorean]

That current flows through a cell doesn't mean that it has a charge, as long as equally much charge flows into the cell as out from it.

In many (most?) cases, the current flows as a result of the charge imbalance (as well as concentration imbalances). In fact, the "membrane potential" is defined as the difference in potential across the membrane (i.e. inside vs. outside the cell) and this is, of course, a result of the charge imbalance between the two regions. This is one of the ways in which organisms store energy.

And although it may happen that some neighboring cells may be charged (but not very big charges, I think) an organism as a whole is rarely charged (exceptions may perhaps exist, such as electric eels). I am certain that my own total charge is negligible.

But you're changing the subject now from cells to whole people now so I'm not sure what your point is.

 

[Simon Bridge]

If cells were typically electrically charged, they would attract and/or repel each other, and that is not what we typically see...

Who is this "we"?
What reason do you have for believing this statement?

What I mean is - can you point us to a body of research which supports your expectation that cells are electrically neutral - instead of just pulling assertions out of the air.


There are two main purposes to this sort of question:
1. it helps you: when you get used to questioning/verifying your assumptions, you find yourself learning more and faster, and you will get taken seriously more;
2. it helps us to help you: when you provide a reference it helps us understand how you are thinking and thus how best to help you quickly.

You have to look carefully to see the electrical repulsion and attraction of cells at work
The effects are more obvious when lots of the same sort of cell are in solution and an electric field is applied - a quick google yields many examples of charged cells. I'm finding it difficult to support the statement that cells are generally electrically neutral so I am curious as to where you got the idea from.

That current flows through a cell doesn't mean that it has a charge, as long as equally much charge flows into the cell as out from it. And although it may happen that some neighboring cells may be charged (but not very big charges, I think)

... do you have reason to think that the charges are not very big? i.e. have you seen a study that measures the electric charge of a cell of some kind (there are lots of different kinds...)?

"Big" is a comparative term - it is not clear to me what you are comparing to.

... an organism as a whole is rarely charged (exceptions may perhaps exist, such as electric eels). I am certain that my own total charge is negligible.

Do you have a reason to be so certain?
When did you last measure your own total charge?

The human body is regularly charged up to 2-3kV, depending on the time of day and what you've been doing - you'll also be aware that human skin has a pH of around 5.5, indicating surplus H ions (acid). Although this is more to do with gaining or losing ions to the environment than the accumulated effect of individual cells, it does count against the idea that an organism as a whole is neutrally charged.

It is also irrelevant to your initial question: let's say that an organism as a whole is neutrally charged - that just means that there are roughly equal amounts of positive and negative charge in the organism. It does not mean that individual cells cannot carry a net charge.

To let you off the hook:

Individual cells, like fat cells or platelets say, are typically negatively charged ... the blood plasma tends to be positive. The result is a potential difference across the cell membranes. This potential can be an important part of how cells interact.

I don't want you to think I'm pulling this stuff out of the air:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141459/
... measuring the net charge of red blood cells in mammals (as an example of a biological cell).
There are lots of different kinds of cells, so you may need to be more specific in future.

I believe your original question has been answered though.
The point of all above is to try to improve your ability to ask questions in future.

 

[Erland]

Individual cells, like fat cells or platelets say, are typically negatively charged ... the blood plasma tends to be positive. The result is a potential difference across the cell membranes. This potential can be an important part of how cells interact.

I don't want you to think I'm pulling this stuff out of the air:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141459/
... measuring the net charge of red blood cells in mammals (as an example of a biological cell).
There are lots of different kinds of cells, so you may need to be more specific in future.

Ok, thanks.

According to your link: "a single mammalian red cell has a net surface charge ranging from four to fifteen million electrons, depending on the species".
Now, this is the charge of only the surface of the cell, but let us assume (and correct me if this is totally wrong) that the net charge of an average human cell (surface + interior) lies somewhere near this range (atlhough the link only mentioned red cells).

Also, a typical human cell contains about a billion ATP-molecules. Since ATP is a ion with charge -4 (4 electrons), this means, if the assumption is correct, that the total charge of the ATP-molecules in a human cell is about 300 or more times greater than the net charge of the cell. Therefore, there must exist other ions/particles which neutralize the vast majority of these ATP-molecules. Which are those ions/particles?
My guess is that it is mainly hydrogen ions, but that is only a guess.

 

[DiracPool]

Ok, thanks.
Therefore, there must exist other ions/particles which neutralize the vast majority of these ATP-molecules. Which are those ions/particles?

Why are you so focused on the static charges of biological cells, are you worried you're going to spontaneously combust or something? Lol.

Again, as I mentioned in my last post, your assertion that "the cell as a whole is neutral" is oversimplistic as is your thesis here that the cell needs agents to "neutralize" electrons or ATP in order to avoid catastrophe.

The answer to your question, again, is that the cell maintains a disproportionate gradient of charge via the flow of electrons and protons (H+), depending on its energy needs. It does so through the electron transport chain, where free electrons are "traded" between various molecules in Redux (reduction-oxidation) reactions in order to establish particular electrochemical gradients in the cell that allow it to do work. From: http://en.wikipedia.org/wiki/Electron_transport_chain

The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor passes electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by actively “pumping” protons into the intermembrane space, producing a thermodynamic state that has the potential to do work.

So, the biology of the cell is NOT organized as to provide it with agents that simply "neutralize" negatively charged molecules or free electrons, there is dynamic process that is going on here.

As far as this comment you made:

If cells were typically electrically charged, they would attract and/or repel each other, and that is not what we typically see...

Again, this is a naive and oversimplistic notion of how cellular assemblages work. Cells are embedded in tissues that are held together through cellular adhesion molecules that easily overcome any electrochemical forces between cells: http://en.wikipedia.org/wiki/Cell_adhesion

In the brain at least, these electrochemical potential differences are important to the function of the system, not detrimental. They do not act by one neuronal cell "pulling" or "pushing" on another, they work collectively, with these potentials passing through and spanning hundreds or even thousands of neurons simultaneously. This is what we see in EEG and EoC tracings.

 

[Mike H]

As has been noted, cells are hardly at any sort of true equilibrium. If they were, they'd be dead.

Having said that, I think perhaps, as an illustrative example, the following article will be able to put your mind at rest in terms of what's floating around a typical cell. Enjoy!

 

[Simon Bridge]

...there must exist other ions/particles which neutralize the vast majority of these ATP-molecules. Which are those ions/particles?

Why? What do you think would happen if there weren't?

My guess is that it is mainly hydrogen ions, but that is only a guess.

You mean that the researched net charge appears smaller than woud be indicated if the ions you names were not somehow neutralized? But what is wrong with just having the same number of positive and negative ions? i.e. if there are about the same amount of NAD+ as ATP and ADP together, you'd get a net neutral charge for these molecules alone.

The lit on cell membrane potentials suggest sodium ions in the blood plasma provide the positive charges in blood... however, look it up and you'll see that bacteria and amoebas tend to be negatively charged too.

The gripping hand is: the particular net charge is a result of all the chemicals and chemical processes that exist and occur in and around the cell. There's millions of them depending on the cell. There is no specific neutralizing agent for specific ions and there is no need for any.

 

[atyy]

You mean that the researched net charge appears smaller than woud be indicated if the ions you names were not somehow neutralized? But what is wrong with just having the same number of positive and negative ions? i.e. if there are about the same amount of NAD+ as ATP and ADP together, you'd get a net neutral charge for these molecules alone.

The lit on cell membrane potentials suggest sodium ions in the blood plasma provide the positive charges in blood... however, look it up and you'll see that bacteria and amoebas tend to be negatively charged too.

The gripping hand is: the particular net charge is a result of all the chemicals and chemical processes that exist and occur in and around the cell. There's millions of them depending on the cell. There is no specific neutralizing agent for specific ions and there is no need for any.

If you look at the Sigma catalogue, ATP is sold as a disodium salt http://www.sigmaaldrich.com/catalog/product/sigma/a2383?lang=en&region=US . So here the counterion is sodium in artificial ATP. I think the OP is asking about the typical counterions for ATP in the cell.

 

[atyy]

In many (most?) cases, the current flows as a result of the charge imbalance (as well as concentration imbalances). In fact, the "membrane potential" is defined as the difference in potential across the membrane (i.e. inside vs. outside the cell) and this is, of course, a result of the charge imbalance between the two regions. This is one of the ways in which organisms store energy.

The charge imbalance is only in a small region around the membrane. If you average across the membrane, the cell is neutral. It's like equal and opposite charge on the two plates of a capacitor - each plate is charged, but the capacitor is neutral.

 

[Simon Bridge]

If you look at the Sigma catalogue, ATP is sold as a disodium salt http://www.sigmaaldrich.com/catalog/product/sigma/a2383?lang=en&region=US . So here the counterion is sodium in artificial ATP. I think the OP is asking about the typical counterions for ATP in the cell.

... well in blood, the sodium is typically outside the cell, hence the membrane potential.
But sure - if that is the question, then Na+ would be a reasonable answer, though, considering the reasoning, I'm concerned it is misleading...

How about it Eriand, is that what you wanted to know?

 

[atyy]

... well in blood, the sodium is typically outside the cell, hence the membrane potential.
But sure - if that is the question, then Na+ would be a reasonable answer, though, considering the reasoning, I'm concerned it is misleading...

How about it Eriand, is that what you wanted to know?

How about something like Mg⁺⁺, maybe for specific steps? Eg. http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/glycolysis.htm "The positively charged Mg⁺⁺ interacts with negatively charged phosphate oxygen atoms of ATP, providing charge compensation and promoting a favorable conformation of ATP at the active site." This site has a diagram http://guweb2.gonzaga.edu/faculty/cronk/biochem/A-index.cfm?definition=ATP .

 

[Simon Bridge]

How about something like Mg++,...

... or, indeed, anything that may happen to be present.
We are back to the "no specific neutralizer" answer.

 

[DiracPool]

The charge imbalance is only in a small region around the membrane. If you average across the membrane, the cell is neutral. It's like equal and opposite charge on the two plates of a capacitor - each plate is charged, but the capacitor is neutral.

That's not entirely correct, unless maybe you're talking about an isolated cell in vitro. Pythagorean, I believe, was talking about neuronal membrane potentials, which sum across and through mm, even cm of neuropil. The synapses on the dendrites of neurons act as mini batteries whose excitatory current loops into the neuron from the synapse, through the axon hillock, out into the interstitial matrix, and then back into the cell through the same synapse. Inhibitory current loops in the opposite direction. If we are talking about an inhibitory synapse, we have a local hyperpolarization of the membrane through the influx of, typically, chloride ions and the efflux of potassium ions. If the synapse is excitatory, we have a local depolarization of the membrane through the infux of sodium ions. It is the summation of tens of thousands of these competing synapses geographically dispersed about the dendritic tree of the neuron and even cell body itself that trigger an action potential through voltage-gated ion channels. The pulse frequency of individual pulses and pulse density of populations of pulses is directly proportional to the potential voltage difference across a population of neurons in a target region. The potential fluctuations/oscillations in one region, of say, neocortex, versus another can be quite substantial and show up as "bursts" of activity in some regions, and quieter "background" activity in others.

Incidentally, this is the reason that cortical neurons are arranged in vertical columns and hypercolumns. They are arranged this way in order to leverage the geography of the current flow through dendritic arbors in order to facilitate these collective, metastable burst patterns.

Thus, if you are talking about the charge imbalance across the membrane of a neuronal cell in vivo embedded in a population in a healthy brain, the charge imbalance across the cell membrane is not confined to a small region around the membrane and it certainly does not average out to being neutral. These imbalances are read out as the local field potentials that surround these neurons.

See this article: http://soma.berkeley.edu/archives/ID6/92.html

 

[Erland]

It was perhaps unwise of me to use word "neutralize", since that indicates some kind of action by some kind of agent. Some of you seem to believe that I meant something like that. I didn't.

What I mean is simply this: If the typical net charge of a cell is at most 15 millions units of elementary charge (positive or negtive) and if there is a billion ATP-molecules in the cell, each with a net charge of -4 units of elementary charge, then there must be other particles/ions in the cell with a total charge of at least +3.985 billions units of elementary charge. This is simply a logical consequence of the assumptions (based on the article Simon linked to). So I just wonder which these positively charged particles/ions are.

It could of course be that NAD+ balances a substantial part the ATP but to me, this does not seem very plausible, since this seems to indicate some kind of connection between ATP and and NAD+ which I am unaware of.

Sodium and magnesium ions have also been suggested in the thread, and this seems more plausible to me. After all, the phosphorus in ATP must ulimately come from food (unless it is present in very large amount at birth and then becomes diluted as we grow, but this does not seem plausible), and phosporus in the food might come from salts such as sodium phosphate and magnesium phosphate.
My own guess, that the "counterions" (good word, never heard it before) are mainly hydrogen, is less likely. I thought it came from phosphorus acid, but I don't think we ingest so much of that (again, correct me if I am wrong).

I will look at the links you people gave more closely, but I now consider the question of the counterions to ATP as anwered. Thanks for that, all!

So, now remains the question of the counterions in the cell to NAD+...

 

[atyy]

... well in blood, the sodium is typically outside the cell, hence the membrane potential.
But sure - if that is the question, then Na+ would be a reasonable answer, though, considering the reasoning, I'm concerned it is misleading...

How about it Eriand, is that what you wanted to know?

It was perhaps unwise of me to use word "neutralize", since that indicates some kind of action by some kind of agent. Some of you seem to believe that I meant something like that. I didn't.

What I mean is simply this: If the typical net charge of a cell is at most 15 millions units of elementary charge (positive or negtive) and if there is a billion ATP-molecules in the cell, each with a net charge of -4 units of elementary charge, then there must be other particles/ions in the cell with a total charge of at least +3.985 billions units of elementary charge. This is simply a logical consequence of the assumptions (based on the article Simon linked to). So I just wonder which these positively charged particles/ions are.

It could of course be that NAD+ balances a substantial part the ATP but to me, this does not seem very plausible, since this seems to indicate some kind of connection between ATP and and NAD+ which I am unaware of.

@Simon Bridge, I think Erland's understanding is similar to yours? It doesn't seem he's asking for so specific a counterion, just for example, whether it is sodium, magnesium, hydrogen etc.

Sodium and magnesium ions have also been suggested in the thread, and this seems more plausible to me. After all, the phosphorus in ATP must ulimately come from food (unless it is present in very large amount at birth and then becomes diluted as we grow, but this does not seem plausible), and phosporus in the food might come from salts such as sodium phosphate and magnesium phosphate.
My own guess, that the "counterions" (good word, never heard it before) are mainly hydrogen, is less likely. I thought it came from phosphorus acid, but I don't think we ingest so much of that (again, correct me if I am wrong).

I will look at the links you people gave more closely, but I now consider the question of the counterions to ATP as anwered. Thanks for that, all!

So, now remains the question of the counterions in the cell to NAD+...

@Erlang, I wouldn't take my suggestions as anything close to final. I thought your question was reasonable, and was just trying to explain it (maybe) a bit to Simon Bridge. To be honest, I had guessed hydrogen too. I don't understand the sodium answer - sodium is high in the extracellular fluid, but is that also the case in the cell?

 

[Ygggdrasil]

1) Let's say you have water and you mix in some sodium chloride and sodium acetate. In the solution, what ions are neutralizing the sodium? The sodium ions exist surrounded by a solvation shell of water, and do not interact with either the chloride or acetate ions in solution. Basically all of the negative charges in the water (the chloride and acetate ions) are helping to neutralize the charge of the sodium ions. So, when you ask what ions in the cell neutralize the charge of the ATP, the answer is all of the positively charged substances in the cell.

2) Now, we've reduced the question to one with a much clearer answer: what are the main charged ions present in the cell? The following wikipedia page is probably relevant for this discussion: http://en.wikipedia.org/wiki/Cytosol#Ions

Potassium is the primary cation present inside cells. Most of the negative charge inside of cells is probably accounted for by the proteins (which tend to have an overall negative charge) and DNA. Calcium and magnesium are important cations within the cell (and regulate many important proteins), but these cations are often bound by proteins and thus the free concentrations are quite low.

 

[atyy]

@Ygggdrasil, would the answer be different depending on whether the ATP is in the cytosol or a mitochondrion, or is potassium also the major cation in mitochondria?

Also, how about the magnesium which googling about seems to indicate is coordinated with ATP, at least in the cytosol? Does that mean that magnesium is associated with ATP more closely than the ratio of free magnesium to potassium ions would suggest?

 

[Ygggdrasil]

I'm not aware of any mechanisms that would cause potassium to not be the major cation in mitochondria, but a quick search didn't yield any good sources describing the concentrations of ions in the mitochondrial matrix.

I have also heard that magnesium ions are coordinated by the triphosphate group of nucleotides (and this would make some sense because most enzymes that use nucleotide triphosphates require magnesium as a cofactor), but this is probably a special case.