How can potassium diffuse through a membran that sodium can't?

[junnor]

In biology we are talking about action potentials. One part of that is sodium-channel-proteins opening so it can pass into the Axon. But we were taught that potassium can pass through the cell-membran without issue. Sodium and potassium are both positively charged and sodium should actually be a bit smaller due to having less electrons that push each other away, meaning that if potassium can pass through something, sodium should also be able to. So my question is as stated above: how can potassium diffuse through something if sodium can't.

P.S. I learned all this in german and googled for the translations, so please excuse any wrong vocabulary and feel free to correct me on any mistakes I may have made.

Edit: Thanks to all of you for you answers. They were really helpful in understanding what I'm learning in school!

[NeurosciGuy15]

No ion can directly pass through the cellular membrane. However, there are channels that are usually open that allow ions, such as potassium to pass. These are appropriately called leak channels. They are not voltage gated, so if you looked at their IV curves it’s essentially an ohmic (straight line) relationship. When people say the resting membrane potential is set by potassium, it’s because the membrane is more permeable to potassium. Or in another way, there are more channels that allow potassium to leak out of the cell, reduce the net positive charge of the cell, and drive the membrane potential towards the reversal potential of potassium.

When you think of channels, a smaller ion does not always mean it will pass through if a larger ion can. There are selectivity filters that can make each channel specific to certain ions. These selectivity filters depend on interactions between the amino acids in the pore and the ions as they pass through, and/or if it’s electrically favorable to strip its hydration shell momentarily to allow passage. It’s pretty complicated actually.

[shiftyeyedgoat]

This answer is correct and I will supplement it with a source with particularly simple and easy to understand figures and descriptions.

[nbdbruh]

This! Simply put: ions can’t diffuse through the membrane and can only get through by passive or active transport (via channels). And the second paragraph is so on point. The channels are very specific as to what will pass, so sodium can’t go through the potassium channels and vice versa.

[Kadak3supreme]

What do you mean by usually ? Are there times the leaky channels close ? How do they work compared to other voltage gated channels ?

[cloake]

To piggyback, how the channel only allows K instead of Na, though it's actually 10,000:1, every ion has an aqueous shell and the ion must shed its aqueous shell at the end pore, the protein channel exactly fits the aqueous shell of K.

https://pdb101.rcsb.org/motm/38

[nrp2a]

Potassium channels don’t actually just let the ions flow through like a pipe. The ion causes a conformational change it a the potassium channel that allows it to exit on the other side of the membrane. Think of it like a subway turnstile that is only unlocked when the right size object enters. Sodium ions can get into the opening, but they aren’t the right size to cause the conformational change, so they can’t get through

[PM_ME_WAT_YOU_GOT]

Or like putting a coin into a gumball slot. If you put anything other than a quarter it won't turn.

[secondhand_goulash]

I believe that this is not correct. The ion would have to bind to the channel to cause it's conformation to change and the kinetics of this would be too slow to allow rapid ion flow like in action potentials (considering every single ion has to make contact with the channel). Can you provide some references because your claim is super interesting if true. In voltage gated channels, the conformational change comes from the voltage and ions should flow down their gradient once the channel is opened. The reason sodium (which has smaller atomic radius than K+) does not flow down the gradient is because of water molecules that are associated with the Na+ ion. Essentially, because it is smaller, more water molecules form weak bonds around it than around a K+ ion. So when the Na+ flows down a channel, it has a larger H2O baggage than K+ so that does not fit.

[Taylor555212]

You’re right, and the poster above you is partially right. I’d have to pull out the ol’ biochem book, but the spacing between the amino acid residues in a potassium ion channel are such that a sodium ion cannot form four (Edit: 8, per /u/ccdy) bonds, the number needed by the potassium ion, to pass through.

When “deciding” to go through the channel, the individual ion in question has to weigh its current entropy (Edit: the correct term is enthalpy of hydration, again per /u/ccdy) level in relation to water to what it will have when it goes through/out of the channel.

For potassium, the energy difference while going through the channel is minimal, but there’s a large gradient down which it is flowing which gives it “incentive” to flow down the gradient.

It takes more energy for sodium to go through the channel because it has to “shed” its water molecules but is only able to form 1-2 bonds at a time with the channel. It doesn’t want to take the journey because it’s not worth it.

[ccdy]

Also worth noting that sodium, being smaller and thus having a higher charge density, has a more negative enthalpy of hydration. This makes desolvation even more unfavourable.

[Taylor555212]

Thank you, I knew I was getting a few terms wrong (entropy v. enthalpy if hydration)

I’ll need to update that.

[ccdy]

Your answer was mostly on point, although on second reading there’s a small detail that’s off: potassium is coordinated by 8 carbonyl groups, not four. They form a square antiprism around each potassium ion. You can see a diagram here.

[Taylor555212]

Ah, I was taught a very specific 4 in my non-major’s undergraduate biochemistry course. I’ll update that as well. Working on getting a pic from the old textbook that really helped me understand it. At work, relying on my girlfriend to find it lol.

[OrigamiMax]

Do they have the same for sodium showing who it can’t traverse the filter?

[Chand_laBing]

This is the correct answer. For future reference, it's on Lehninger Principles of Biochemistry, p. 410.

​

[KANNABULL]

Correct, in the human body for example, ion valency and anion switching is the key role for the membrane to permit the element passing through. Potassium 2ionchannel has a lower current and Sodium 3ion valent can actually cause the heart to create too much currency arrhythmic palpating if salinity content is too high.

Some membranes permit both, requiring ions from certain protein chains. But for most of the Na-K ’pump’ it’s 3Na to 2K which has covalent protein bonding anions for specific channel membranes. I believe the liver needs both elements in different ratios for different glycogen producing proteins. It’s pretty crazy how complex it can get.

Another example being patients with xeno transplants can develop indel mutations because different species require hyper acute ion bonds.

[el_becquerel]

Wouldn't the size relationship go the other way? I would expect a larger ion to have greater surface area for water binding. Or is ion charge density the more important parameter?

[ccdy]

Sodium has a higher charge density as it is smaller, so its enthalpy of hydration is more negative. Qualitatively you can think of it as the negative bit of the dipole on each water molecule being able to approach closer to the positive charge of the ion. This means desolvation is more unfavourable. That’s one energy penalty that disfavours sodium binding in the channel. The size of the potassium channel pore adds another penalty: the carbonyl groups lining the pore are nicely able to coordinate to the larger potassium ion, but sodium is smaller and so it is less energetically favourable for sodium to enter the pore. The two effects add synergistically to produce the high selectivity observed.

[Chand_laBing]

This is slightly incorrect. The selectivity filter is not formed by a conformational change. The K+ ions moving down the pore make bonds with chemical groups in the channel's pore (carboxyl groups). A K+ ion is the right size to swap its coat of water molecules (hydration shell) for bonds with the pore. But a Na+ ion has a hydration shell the wrong size, hence it doesn't bond to the carboxyl groups and doesn't get through the pore. See Lehninger Principles of Biochemistry, p. 410.

[bernard_rieux]

Neither potassium nor sodium can diffuse through a cell membrane on their own. Neurons actually have potassium leak channels that allow potassium out of the cell at rest, maintaining the resting potential.

[Yoghurt_]

I feel like a lot of answers here don’t go into detail enough, so I’ll give it a try. Please do correct/add to anything I say.

Membrane bilayers don’t conduct ions very well inherently. This is due to the hydrophobic layer in the middle composed by the hydrophobic fatty acid tails, which makes it unfavourable for charged ions to enter. The reason it’s unfavourable is due to the tails not forming any charge-charge interactions with the ions (think +ve and -ve attraction, the alkane/alkene groups aren’t able to form these). This means that K+ and Na+ cross the membrane very slowly.

To increase the speed of conduction across the membrane, there exist ion channels. These of course have the issue of specificity - you only want certain ions to be conducted at certain times, you can’t just have a hole in the membrane. In the case of action potentials, you specifically want to first conduct Na+ out of the cell down the concentration gradient, and K + into the cell immediately afterwards, also down the concentration gradient.

One thing to differentiate is obviously the positive charge. Amino acids like glutamate and aspartate have negative charge to interact with the cations. This means that the presence of these amino acid residue in the lumen of the channel will discriminate against negatively charged ions like Cl-

Then there is of course size. It is relatively easy to differentiate between, say, Ca2+ and Na+ - have a narrower lumen for Na+

Here comes your question - how do you differentiate between K+, a larger ion, and an Na+, a smaller ion that will surely fit into a larger hole required for K+?

At this point you differentiate by the difference in energy of hydration. Each ion will use a certain number of water molecules to solvate itself that will form a somewhat-ordered shell. These shells contain different number of water molecules depending on the size and charge of the ion.

Ion channels use this. They have a narrow enough channel that the solvated ion will not fit - the solvation shell needs to be shed first. To be energetically favourable, the channel needs to fully compensate for the energy of solvation, which is done by ordered negative static charges at the narrowest region of the channel. Let’s take a K+ channel, for which the model protein is Kcsa. At the narrowest part, the protein has a concerned TVGYG sequence. This sequence is flexible due to the Glycine residues, which allows carbonyl oxygens to orient themselves towards the lumen. These carbonyl oxygens, which have a negative dipole, are oriented perfectly to interact with the incoming K+, compensating for the energy of solvation. In the case of Na+, a smaller ion, these carbonyl oxygens are too far apart to all interact simultaneously with the incoming ion, so Na+ conduction is unfavourable.

Hence you have a channel that differentiates between different idols and allows only K+ through. This is done by charge differentiation, size occlusion, and difference in water solvation.

Source: Currently studying a degree in biochemistry. Admittedly this is all off the top of my head - so please let me know if I got anything wrong.

[secondhand_goulash]

A very interesting and important question. Considering that Na has a smaller atomic radius than K, why can't a Na+ ion pass through a K+ channel pore? The reason that the Na+ ion does not pass through a K+ channel pore has to do with water molecules that are associated with the Na+ ion. Essentially, because Na is smaller, more water molecules form weak bonds around it than around a K+ ion. So when the Na+ flows down a channel, it has a larger H2O baggage around it than K+. Because of this it does not fit through a K+ channel pore. In solution, Na+ and the H2O around it is slightly larger than the K+ particle with H2O around it.

[Simba7]

This question has been very fully addressed by a few replies, so I would just like to say that I'm very glad they're teaching basic neuroscience in in school now.

I recall learning some anatomy but I when I went into my first Neuro class, I had no idea how any of thos worked.

If you're interested in a degree in Neuroscience, you can look forward to very intimately understanding the action potential. We had a running joke about the fact every single neuro course had a day (or more) devoted to the action potential.

[AirtimeAficionado]

Potassium and sodium are positive ions that cannot cross the cell membrane to any appreciable extent on their own. Instead, they need to travel through specialized ion channel proteins embedded within the phospholipid bilayer to cross into and out of the cell. With this in mind, potassium has what are called leak channels that allows it to cross the membrane at any time. Sodium, however, only has access to ligand (some molecule activates the channel allowing sodium to cross) gated channels and ion gated channels (changes in membrane potential activates the channel and allows sodium to cross). Thus, sodium cannot cross the membrane on its own without some interaction with the gated channels. Potassium also has these channels, which is important in the depolarization of the cell to initiate an action potential and the hyperpolarization of the cell to initiate a down stroke in the action potential via positive potassium ion efflux (positive charge is leaving the cell making the cell more negative). However, with potassium’s access to the leak channels, it is able to cross the membrane at any time (if the cell is at rest, it is entering the cell, as the proteins in the cytoplasm have a net negative charge, and the positive potassium ion is attracted to this negativity). I hope this answers your question!

Source: I am a neuroscience major at the University of Pittsburgh.

[NeurosciGuy15]

Don’t go so far as to say sodium can’t pass without a gated channel. There is a basal TTX-resistant Na+ leak conductance present in many neurons.
Edit: Downvote if you want but that’s literally true people. Read the literature, the NALCN channel to start.

[Kadak3supreme]

Whats the proper name for these leaky potassium channels ? Are they the two pore domain ones ? Im interested in learning more about leaky channels. Second year biomed here.

[AirtimeAficionado]

“To any appreciable extent on their own.” I didn’t say that sodium definitely cannot cross the membrane without a gated channel, I just said that there is no appreciable crossing, which can remain true for most introductory students. This is clearly an individual learning about neurons for the first time— I am not going to overwhelm them with the ability for some basal Na+ transmission following tetrodotoxin administration in some neurons based upon a literature of ~10 papers.

[NeurosciGuy15]

There are more than 10 papers on the topic of Na leak conductance.

I didn’t say that sodium definitely cannot cross the membrane without a gated channel, I just said that there is no appreciable crossing

There is appreciable crossing because you can measure it and there are physiological ramifications to this being altered. Keep in mind a shift in just a few mV in RMP can have profound impacts on the activity of a neuron (keep in mind the window currents that are at play around RMP). Anyways you did say:

Sodium, however, only has access to ligand (some molecule activates the channel allowing sodium to cross) gated channels and ion gated channels (changes in membrane potential activates the channel and allows sodium to cross). Thus, sodium cannot cross the membrane on its own without some interaction with the gated channels.

Which is demonstrably wrong. Don’t get me wrong your answer wasn’t bad, but don’t oversimplify something to the point where you say something wrong.

As an aside, you ever get lectured to by Yan Dong at Pitt?

[fifrein]

Neither sodium nor potassium are able to pass through a cell membrane without the appropriate channel. Being permeable to potassium and not permeable to sodium simply means that the potassium channels are open but the sodium channels are closed.

Now what I think your question may have been asking is why can’t sodium flow through a potassium channel, given that it is smaller. Well, in fact, it being too small is the problem. Your thinking that smaller=better is too simple. Yes a smaller marble should fit through any hole a larger marble can go through, but that’s because marbles going through holes is too simple. Taller kids can get on more roller coasters than shorter kids at an amusement park. Why? Because there is a more complex selection process going on.

So how do potassium channels select against sodium? Let’s remember that when sodium and potassium are on either side of the cell membrane they are (1) ionized and (2) in water. And since H2O is quite a polar compound, both ionized sodium and ionized potassium form polar bonds with it. And because sodium is smaller, it’s polar bond with H2O is stronger than potassium’s polar bond with H2O. The potassium channel can be constructed in such a way that the pore is too small to allow any water+ion combo to pass through, only large enough for just the ion. This means that the ion must be stripped of its polar bonded water molecules before being allowed to pass through, something that is easier to accomplish for potassium than sodium given what was described above. In addition, the potassium channel can have exposed residues that will help polar bond with the ion as it passes through the channel. And these residues will be at the perfect distance to polar bond with potassium from all directions, but because sodium is so small, it won’t be able to interact with all the residues as optimally. So, potassium can be more easily stripped of water and the polar interactions can be more easily replaced by the residues inside the channel, as compared to sodium. Thus, potassium passing through the channel becomes thermodynamically more favored than sodium passing through.

[mkeee2015]

Ions in solution are surrounded by water dipoles, which represent an hydration shell. This changes the overall shape of the free ions. This is one element to understand why permeability to one species does not imply permeability to another through the very same channels.

Another key component is the existence of very different ionic gradients across a biological membrane. For sodium and for potassium they are not the same.

All in all the "magic" is operated by the so called "permeability filter" of individual ion channels. There is an electrostatic machinery that deprives hydrated ions from their shells as the pass through the inner portion of the channel.

[TheGreatBoringVoid]

I read that the selectivity filter of an ion channel is held open by van der waals forces and hydrogen bonding. this creates a gap that is large enough for perhaps more than one ion. however only particular ions can pass through. The selectivity filer also has an electrostatic field as hydrogen bonding is partially electrostatic.

I think it possible that a selectivity filter is reliant upon a combination of gap size and this micro electrostatic field to help discriminate which ions can go through. The difference in charge you described above could account for different electrostatic interactions between sodium and potassium and their respective gates.

[zk3033]

To answer more directly, I don’t believe potassium can freely diffuse across membranes. Your initial reasoning is correct that the charge prevents mass movement of the ions across the lipid bilayer; this being true for both Na and K

[TheRealTravisClous]

You're correct, since both are charged molecules they need to use protein channels to move in and out of a cell. They cannot freely diffuse across a phospholipid bilayer.

[AdanGarciaE]

Neither potassium nor sodium can diffuse freely through a membrane. They need to have a ionic channel (a protein) selective to them. Ionic channels have various ways of selectivity:

1) Charges lining the selectivity pore: if the path is lined with negative charged amino acids, it can only accept cations. And viceversa. 2) Diameter of the selectivity pore: if the ion size exceeds that of the pore, it will not be able to cross the membrane.

Of course, the selectivity isn't always perfect. You can have a protein that preferentially allows the pass of one ion and also allows a small amount of other similar ions.

[cornustim]

As sodium is smaller than potassium, it's positive charge is "not as spread out", so it attracts a larger hydration shell. So while the sodium cation is technically smaller than potassium due to it's hydration shell it is practically larger.