BK Channels And Diet

Kidneys are the main regulator of fluids, potassium and sodium in our bodies. They make up for variations in the diet of the amount of fluid, potassium and sodium that we take in. There are limits to how well they can regulate this, though. The limits are related to the type of environment in which we evolved over thousands of years. That environment had food with a lot of potassium and very little sodium. How do the kidneys do this?

How Kidneys Balance Potassium And Sodium

The kidneys perform this balancing act by using multiple types of channels and pumps in their cells. The main channels are the potassium channels and the sodium channels, since these are the two main ions that are used to create a changing electric field that drives cell processes.

The pumps are mostly powered by ATP. These pumps can move various types of ions against their concentration gradients to continually restore the cell's resting condition. The entire process is like letting a ball roll down a hill (how the channels work) and then using a machine (expending energy through ATP) to push the ball back up the hill, so the ball can roll down again.

BK Channels

One of the channels that has been extensively studied is a potassium channel known as the BK channel. It is found in abundance in the kidney. The BK channel comes in many variations.

But the variations all have two components. One component is named alpha (BKa) and one is named beta. The beta subunit has 2 variations in the distal nephron of the kidney- beta1 (b1) and beta4 (b4) (b2 and b3 occur in other cells).

The number of BK channels is increased in the kidneys of those on a high potassium alkaline diet. This allows the kidneys to excrete more potassium in the urine.

BKa/b1 is located in connecting tubule cells of the kidney, and passes potassium into the tubule of the nephron. BKa/b1 is found mostly in the principal cells (PC) in the connecting tubule. The absence of BKb1 leads to hyperaldosteronism, hyperkalemia, fluid accumulation, and hypertension. People with this condition are made worse on a high potassium diet.

BKa/b4 is the second kind of potassium channel in the distal nephron. It is more abundant than BKa/b1 and is located in the intercalated cells (IC) of the connecting tubule and collecting ducts that eventually lead to the bladder. The presence of BKa/b4 promotes potassium excretion when the diet is alkaline, high in potassium and low in sodium.

The Study

In this study (1), the researchers sought to find out what factors influenced the ability of BKa/b4 to increase potassium secretion when someone is on a high potassium alkaline diet. They looked at BKa and b4 separately.

Normally BKa is made near the nucleus of the cell. It then moves through the cytoplasm to the cell surface that lines the tubule that carries urine eventually to the bladder. The researchers blocked aldosterone and found that when aldosterone is blocked, less BKa is made. The researchers found that less total BKa was in the cell, and that less potassium was able to be excreted.

The proportion of BKa at the tubular surface versus the proportion in the cytoplasm was the same as when aldosterone was not blocked, though. So aldosterone affects how much BKa is made. But aldosterone does not affect the proportion of BKa that gets to the cell surface. This effect was the same whether the urine was acid or alkaline.

When the researchers examined effects on b4, they found that aldosterone had no effect on b4. However, they found that when urine was alkaline, more b4 was made by the cell. They found more b4 inside the cell when urine was alkaline than when urine was acid.

And they found that a higher proportion of BKa made it to the tubular surface of the cell when there was more b4 present. They concluded that b4 helps BKa to make it to the surface of the cell where BKa (in combination with b4) can excrete potassium.

There's Something About b4

So part of the mystery is solved. We know what structure allows our kidneys to get rid of huge amounts of potassium in our diet. And we know what aldosterone has to do with it. Aldosterone doesn't simply “raise blood pressure.” Among other actions, it promotes the manufacture of BKa to help get rid of potassium. Its effect on blood pressure is related to our diet. If our diet is acid, aldosterone cannot make up for the lack of b4. BKa needs its teammate b4, who only shows up when the diet is alkaline. Then BKa and b4 can combine to get rid of potassium.

But we still don't know why we need b4. Or why an alkaline diet is needed for b4. An alkaline diet is not needed for b1. And b1 can combine with BKa to get rid of potassium. So who needs b4? And what does sodium have to do with all this?

Stay tuned. These same researchers have figured out how and when an alkaline diet can get rid of extra potassium. There is no comparable mechanism for sodium, so it just collects in our body when we get too much. Our bodies think we are still living in caves and won't be able to get salt anytime soon, so they will hang on to it. Our bodies don't know that food manufacturers put it into almost everything. We'll be getting some more at our next meal, and too much every day.
1. Regulation of BK-a expression in the distal nephron by aldosterone and urine pH. Wen D, Cornelius RJ, Yuan Y, Sansom SC. Am J Physiol Renal Physiol. 2013 Aug 15;305(4):F463-76. doi: 10.1152/ajprenal.00171.2013. Epub 2013 Jun 12.

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