Cellular Function And Potassium Sodium Ratio

What you eat determines how well all the cells in your body function. The potassium sodium ratio is the primary determinant of how well your cells function. This is because the potassium sodium ratio determines the electric field across your cell membranes. This electric field determines the shape and function of all the proteins in your cell. It does this by moving potassium and sodium around to change the electric fields in the cell.
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Cellular Electric Fields

Although the general concept has been known for quite a while, the details of these electric fields are only now being discovered. Computer simulations and experimental evidence are demonstrating how the electric field created by the potassium sodium ratio and the local electric fields in the proteins work.

Potassium and sodium are moved in and out of the cell by channels and pumps. X-ray crystallography has shown the atomic structure of some channels in their active state. The active state is when the channels are open, and sodium or potassium is moving through them.

However no such views of the atomic structure of channels in their resting state (when they are closed) have been done. And no views of the channels in intermediate states between the active and resting states are available. But multiple computer simulations have been done to show the missing positions of the channels, and to show how the channels function.

How Potassium And Sodium Control Cellular Electric Fields

The potassium and sodium balance in cells is maintained by channels and pumps. They move potassium and sodium from inside to outside and from outside to inside the cell. In doing so they change the electric field of the cell.

This change in the electric field changes the shape of the proteins that are in the field, much like the changing electric field in an electric motor changes the position of the rotor in the motor. Only, the channels and pumps are much faster than an electric motor.

The change in shape of the protein is how the protein functions. The functional result of the changed shape depends on the particular protein. In the case of voltage gated (VG channels) channels the changing shape of proteins results in an alternation of opening and closing the channel.

Voltage gated channels are protein channels through lipid membranes in the cell that let potassium and sodium (and a few other ions) move through them to go from one place to another. They open and close based only on changes in the electric field they sit in. Each type of channel is unique and lets only one type of ion through. Potassium channels let potassium through. Sodium channels let sodium through.

How A Poor Potassium Sodium Ratio Ruins Cellular Function

However if you do not eat enough potassium, or if you eat and retain too much sodium, you will have a less than optimal balance of potassium and sodium inside and outside your cells. This less than optimal balance will result in a less than optimal electric field to motor your cell processes.

If the electric field is stronger (or weaker) than it should be, then when there is a change in the electric field, the channel protein will have to move more (or less) to perform its function. This will result in taking a longer (or shorter) time to perform its function, and will result in incorrect timing of cell processes. This incorrect timing makes it more likely that the cell will function abnormally.

A Close Look At Channels

At present, x-ray crystallography studies of crystallized channels have shown the shape of some open (active) channels. However the shape of a closed channel has not been seen with x-ray crystallography. And none of the intermediate states between open and closed have been seen with x-ray crystallography.

But computer simulations of the resting state of the channel, and of the intermediate states of the channel, have been done. Multiple different methods have been used to create the simulations. And they have all given remarkably similar results. See http://jgp.rupress.org/content/140/6/587/suppl/DC1 for a beautiful video demonstration.

There was a similar situation in the 1980s when MRIs (also known as NMRs), which are also computed simulations, were done to show protein structures. Later x-ray crystallography studies confirmed these computer simulated models.

It is anticipated that when similar x-ray crystallography studies can be done on the channels, a similar confirmation will occur because there is a remarkable similarity in all of the present computer simulations. Thus there is a high probability that the simulations do correspond to what really goes on in the cell.

The Present Study

The present study (1) is a recent review of how these computer simulations were done, and a comparison of the simulations to show how similar their results are. Each simulation was done by a different group of researchers using different computer methods of molecular modeling, and different template x-ray structures. The results of these simulations showed very similar structures of the VSD (voltage sensing domain) of a potassium channel in its resting state.

Several findings have been confirmed by the similarities in the models. The models have shown that the VSD depends upon salt bridges for its shape. Movement of these salt bridges results in a screw-slide movement of the molecules, resulting in the opening and closing of the pore that lets potassium through. The image above shows the open and closed structures of a channel. More is written about salt bridges here and here.

These simulations also showed that VSDs must move through more resting states before activation when they start from a more negative membrane potential. This means that when the potassium sodium balance has changed, there is a change in how the VSDs function. If the electric field is stronger, the proteins in the gate must move more, and take longer to move, between open and closed. If the electric field is weaker, the proteins will have less movement before the pore will open or close.

Several aspects of the models have been confirmed experimentally. Portions of the VSD structure were later confirmed by experimental data. Distances that were predicted between certain atoms in the structure were also confirmed experimentally. The hope is eventually to see in experiments atom-by-atom movement in the structure over time. This would give experimental evidence to confirm the computer simulations.

The Importance Of The Potassium Sodium Ratio

Thus in addition to the interesting findings about how these channels open and close, the simulations also show the importance of the potassium sodium ratio. When the cellular potassium sodium ratio is not optimal, the electric field will not be optimal. And the movement of the protein in the channels will not be optimal, meaning potassium and sodium movement will not be optimal.

When the movement of potassium and sodium through the channels is not optimal, the timing of the all-important changes in electric field will be off. This leads to mistimed cellular processes and abnormal cellular function.

So we have evidence at the atomic level of how important the potassium sodium ratio is. Epidemiologic studies provided the first evidence. Later evidence came from animal and human group studies. Now at the molecular and atomic level, findings are consistent with the importance of the potassium sodium ratio.

If we do not supply too much sodium, and if we supply enough potassium to our body, our body will provide the correct amount to our cells. This will provide an optimal electric field for the very best function of our cells. However if too much sodium or not enough potassium is supplied, the electric fields in our cells will not be at an optimal level. This will result in less than optimal function of our cells, and less than optimal function of ourselves.

This poor cellular function shows up in assorted ways over various periods of time. The most common way it shows up is hypertension and its associated problems of stroke, heart disease, and kidney disease.
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1. An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations. Vargas E, Yarov-Yarovoy V, Khalili-Araghi F, Catterall WA, Klein ML, Tarek M, Lindahl E, Schulten K, Perozo E, Bezanilla F, Roux B. J Gen Physiol. 2012 Dec;140(6):587-94. doi: 10.1085/jgp.201210873.