The high potassium foods diet can prevent hypertension. But hypertension is a sign of disease rather than a disease itself. The basic underlying disease for primary hypertension most often is the result of a poor potassium sodium ratio of the diet. The disease potentially affects all cells in the body. Researchers are discovering more and more cells that function differently when there is a poor potassium sodium ratio. The publication to be discussed today discusses the role of a certain type of potassium channel in cells that secrete substances in response to various stimuli.
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Two-pore Domain Potassium Channels
The publication (1) is a review of a group of potassium channels, called two-pore domain potassium channels, that are triggered by various stimuli to initiate a series of steps in the cell, resulting in the secretion of a substance. The substances secreted are hormones or transmitters in response to a stimulus.
The most detailed discussion in the study is of two types of cells. One type of cell secretes the hormone aldosterone that is involved in hypertension. The other type of cell secretes a neurotransmitter that is involved with changes in breathing and heart rate.
The article, though, also briefly discusses other cells that function by triggering these two-pore domain potassium channels. These other cells are pancreatic beta cells that secrete insulin, pancreatic cells that secrete digestive enzymes, and heart muscle cells that secrete a peptide, atrial natriuretic peptide.
Carotid Body Cells
The cells secreting the neurotransmitter are cells in the carotid body. The carotid body is located in an artery in the neck. There are special cells in the carotid body that detect oxygen, carbon dioxide, and acidity to send feedback to a center in the brain that influences breathing and heart rate.
There is some debate about which potassium channel in the cell is most responsible for activating the cell processes leading to the feedback signal from these cells. But the process for either channel is to depolarize (lower the voltage, lessen the electric field of) the cell membrane by changing the potassium flow through the channel.
The result of these flow changes is depolarization of the cell membrane. The depolarization sets off a calcium cascade which has a different end result than in the adrenal gland or the other cells mentioned in the article. The result is release of a neurotransmitter that signals the brain center to change breathing pattern.
When the cell membrane is partially depolarized because the potassium and sodium concentrations have shifted, less of a shift in the resting potential of the cell is needed to activate cell processes. For the carotid body, this means the degree of change in oxygen, carbon dioxide or acidity needed to set off the calcium cascade is less.
Hypertension
The role of these channels in hypertension is the second main topic in the publication. Hypertension is related to aldosterone and the renin angiotensin system. It is the interaction of aldosterone with the kidney, and of angiotensin II with the adrenal gland, that affects the potassium and sodium balance in the body. In turn, the potassium and sodium balance affect aldosterone and angiotensin II production.
Aldosterone is secreted from the zona glomerulosa cells in the adrenal gland. It is a hormone secreted in response to 2 main stimuli – the concentration of potassium in the bloodstream and angiotensin II. The electric field (voltage) (polarization) across the cell membrane of the zona glomerulosa cells is changed by these two stimuli.
More potassium or more angiotensin II depolarizes the cell membrane and leads to more aldosterone secretion. The depolarization lets potassium flow out of the cell and sodium into the cell. Less potassium or less angiotensin II increases the voltage and reduces aldosterone secretion. This increase in voltage results in the opposite flow pattern for potassium and sodium.
The authors discuss the two types of two-pore domain potassium channels found in human zona glomerulosa cells – TREK and TASK (2). TREK1 has been found to be active at resting membrane potentials in cows. Cell membranes depolarize in response to angiotensin II in the zona glomerulosa cells in cows, leading to more aldosterone secretion.
TREK1 has also been found in human zona glomerulosa cells, but appears to be less active than either TASK1 or TASK3. In humans, TREK1 is more abundant in other cell types. In these other cell types it not as active at resting membrane potentials and becomes more activated by external stimuli. Thus in humans, it may add to TASK activity under certain stimuli, but has had only limited study in zona glomerulosa cells.
The main two TASK type of channels in the zona glomerulosa cells are TASK1 and TASK3. They appear to be the most active at maintaining resting potential in humans. These channels are inhibited by a high potassium level in the bloodstream and by angiotensin II. The channels normally act by depolarizing the membrane when they are inhibited.
The depolarization leads to an increase in sodium and calcium inside the cell by activating some calcium channels and some sodium channels in the cell membrane. This also leads to a release of calcium from intracellular stores in the endoplasmic reticulum. The result is a calcium cascade leading to more aldosterone secretion.
Secretory Cells
All of these secretory cells have in common the production of a secreted substance in response to an external stimulus that changes the cell membrane's electrical field (voltage) (polarization). Slight changes in the structure of the potassium channel, as discussed here, are responsible for the change in the electrical field. The sensitivity of the channel to different stimuli results in a series of reactions leading to secretion of a substance from the cell.
The actual substance produced by the stimulated cell differs according to the other molecules inside the cell. But the channels all will respond more easily or less easily to their stimuli when the polarization of the cell membrane is changed by a change in concentration of potassium or sodium inside or outside the cell. When the channels are in the zona glomerulosa cells, the result is a chronically elevated secretion of aldosterone. In those on a diet with a poor potassium to sodium ratio, a chronically increased aldosterone secretion leads to hypertension.
How a poor potassium sodium ratio in the diet can lead to hypertension, as discussed here, has been well demonstrated at the cellular and molecular levels. How it can lead to heart failure, as discussed here, has also been well demonstrated at these levels. And how it can lead to poor function in the adrenal gland and a chronically high aldosterone level, as well as poor function in other cells, was discussed in this article.
Many other cellular and molecular studies of other types of cells are consistent with the concept of cellular dysfunction from a poor potassium sodium ratio, although their models may not be as complete as they are for hypertension and heart failure. It is very likely that these cellular dysfunctions also can be prevented by a favorable potassium sodium ratio in the diet.
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1. Role of K2p channels in stimulus-secretion coupling. Kim D, Kang D. Pflugers Arch. 2015 May;467(5):1001-11. doi: 10.1007/s00424-014-1663-3. Epub 2014 Dec 6.
2. Both TASK-3 and TREK-1 two-pore loop K channels are expressed in H295R cells and modulate their membrane potential and aldosterone secretion. Brenner T, O'Shaughnessy KM. Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1480-6. doi: 10.1152/ajpendo.90652.2008. Epub 2008 Oct 14.