A Potassium Channel Hypertension

Hypertension affects over 1 billion people. It contributes to 7 million deaths each year. Inheritance is felt to affect about 30 to 35% of blood pressure levels. The other 65 to 70% is under our control. The controllable aspect is influenced by physical activity, habits and the food we eat.

There are two main components of our food that influence blood pressure levels. Sodium is one component. And potassium is the other. The ratio of these two components inside and outside our cells is what determines blood pressure. What we eat is what determines how much of each component is available.

Genetics And Potassium

Potassium Channel Protein
KCNJ3 Potassium Channel

And genetics is what determines how the available potassium and sodium components are used. The interaction of these components with genetics is what determines the electrical charges within the cell.

You might say “What do I care about the genetics of blood pressure?” The reason you should care is because genetics is what determines how strong a potassium sodium ratio in your diet is needed to generate the proper electrical charges to prevent hypertension and to promote good health. Someone else with different genetics may lower their blood pressure with a diet that has no effect on your blood pressure.

The last post discussed genetic changes affecting how sodium is moved around in the cells (transporter proteins). Another previous post discussed an instance of genetic changes that influenced potassium's effect on the manufacture of aldosterone (one hormone that raises blood pressure when on a Western diet). There's been a recent study (1) of changes in a potassium channel in our cells that affects aldosterone secretion.

This Study

In this recent study the researchers discovered a change in a potassium channel that is a major cause of secondary hypertension. Remember that normally an increase in aldosterone leads to an increase in sodium reabsorption in the kidney and a rise in blood pressure. Normally when there is an increase in potassium outside the cell, potassium will move into the cell.

In certain adrenal gland cells the resulting increase in membrane polarization (the difference in electrical charges across the membrane) leads to less aldosterone secretion. The lowering of aldosterone leads to less sodium reabsorption in the kidney, and thus lower blood pressure. In some people, blood pressure is high and does not come down, because they have a gene that prevents this normal sequence.

Genetic Variants

In this particular study, a gene variant was found that affected part of a potassium channel. The change meant that the channel no longer allowed only potassium to pass. The channel allowed sodium to pass through the potassium channel as well as potassium. This led to a decrease in the membrane polarization and an increase in aldosterone secretion. This increase in aldosterone meant that blood pressure increased.

The researchers found two variants, each of which let more sodium in. One variant was not as severe. It let less sodium into the cell than the other variant did. This less severe variant led to an increased number of adrenal cells, resulting in overgrowth of the cells. However, the more severe variant let in so much sodium that the cells died.

The change in blood pressure was not as bad in people with the more severe variant. The more severe variant resulted in fewer cells left alive to overproduce aldosterone. The less severe variant resulted in more and more cells, so there was more and more aldosterone.

To eliminate other possible explanations for the cell death, the researchers then grew the cells with the more severe variant in culture and did an experiment with the cells. The experiment showed that the cell death was indeed because of too much sodium getting inside the cells.

Although the involved cells died, the individuals with these cells did not die. The researchers felt that nearby immature adrenal cells replenished the dead cells. As the cells matured, they would overproduce aldosterone for a while, and then they too would die. Some cells that overfunctioned may have stayed alive because other mechanisms in the cell compensated for the excess sodium inside the cell. Other studies indicated that this could occur if there were an increase in the sodium potassium pump removing sodium, or if there were a change in the activity of other potassium channels.

Two Concepts

So there are two important concepts that this particular study supports. It supports the importance of the balance of sodium and potassium inside the cell for proper function. And it supports that the variability in blood pressure is related to the function of the potassium channels, as well as the sodium channels and the sodium potassium pump.

The critical variable in each of these cases is the electrical charges across the membranes in the cell. These charges are determined by the potassium and sodium balance in the cell. The potassium and sodium in the cell are determined by the activities of the channels and pumps, and the proteins that transport potassium and sodium.

When the membrane electrical charges change in certain kidney cells, sodium reabsorption is affected, as discussed in the previous post. When the charge changes in the adrenal cells, aldosterone secretion is affected, as discussed in this present post.

When Genetics Meets Diet

Each of us have genes that vary from the genes in other people. Some of these gene variations help some of us to have better protection against hypertension than others have. But it is important for all of us to maintain an optimal potassium sodium ratio.

We can do nothing to change the differences in our genetic makeup. However, if we do not have extreme genetic changes, such as the syndromes discussed in some recent posts, we can control how well our cells function. We can better control how well our cells function by controlling the potassium sodium ratio in our diet. Some of us will find good control with a ratio of 2 and some will need a ratio over 5. However, a satisfactory ratio can be found for the vast majority of us.
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1. Hypertension with or without adrenal hyperplasia due to different inherited mutations in the potassium channel KCNJ5. Scholl UI, Nelson-Williams C, Yue P, Grekin R, Wyatt RJ, Dillon MJ, Couch R, Hammer LK, Harley FL, Farhi A, Wang WH, Lifton RP. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2533-8. doi: 10.1073/pnas.1121407109. Epub 2012 Jan 30.


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