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Coulomb blockade model of permeation and selectivity in biological ion channels

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Coulomb blockade model of permeation and selectivity in biological ion channels
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Biological ion channels are protein nanotubes embedded in, and passing through, the bilipid membranes of cells. Physiologically, they are of crucial importance in that they allow ions to pass into and out of cells, fast and efficiently, though in a highly selective way. Here we show that the conduction and selectivity of calcium/sodium ion channels can be described in terms of ionic Coulomb blockade in a simplified electrostatic and Brownian dynamics model of the channel. The Coulomb blockade phenomenon arises from the discreteness of electrical charge, the strong electrostatic interaction, and an electrostatic exclusion principle. The model predicts a periodic pattern of Ca2+ conduction versus the fixed charge Qf at the selectivity filter (conduction bands) with a period equal to the ionic charge. It thus provides provisional explanations of some observed and modelled conduction and valence selectivity phenomena, including the anomalous mole fraction effect and the calcium conduction bands. Ionic Coulomb blockade and resonant conduction are similar to electronic Coulomb blockade and resonant tunnelling in quantum dots. The same considerations may also be applicable to other kinds of channel, as well as to charged artificial nanopores.
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Transcript: English(auto-generated)
What we are doing is applying physics to biological ion channels and we find that we can reveal several features of channel function that are only explicable in terms of physics.
These include, for example, the selectivity of one ion over another. For example, calcium goes through a calcium channel a thousand times better than sodium, even though the two ions are essentially the same size. We are also able to explain the rapid conduction
because despite the selectivity, the ions go through almost at the rate of free diffusion, in other words, almost as though the channel were an open hole. We can also explain phenomena
in mutation. In our paper, we contend that these effects are all explicable in terms of Coulomb blockade, a phenomenon that also happens in quantum dots. This was an insight due to Igor Kaufman. An ion channel is a very complicated object, contains from thousands of atoms. We claim
that its conduction and selectivity can be explained by simple electrostatics model similar to quantum dots. We consider a simple model of ion channel which is represented
as water filled hole in protein wall. We show in the paper that ion channel represents has zero conduction, which is Coulomb blockade, in the points where captured ions neutralize
QF. A resonant conduction occurs in the middle point between neighboring neutralization points. These equations are identical to those appearing in quantum dots. But the
we definitely need more crucial proofs for our theory and that is what we wait for our friends biologists.
The Coulomb blockade model does appear to explain some very interesting and fundamental observations of ion channel activity. And these are of course fundamental to our understanding of ion channels. Elena will now demonstrate the Patek-Klatt technique. She needs to backfill a glass
electrode with solution of known ion content. By doing this she will control the conditions of the experiment. She also needs to micromanipulate the glass pipette to the plasma membrane of a single cell. And this cell will be expressing an ion channel of choice. The pipette is
connected to a very sensitive amplifier which is able to record ions moving through the ion channel pore and it records them as an electrical current.
Given that the Coulomb blockade model can explain so many features of biological ion channels, features that were previously not understood, we physicists are confident that it's correct and that it will be validated by the experiments being done by Elena and Stephen. For details please read our paper.