Discovery reveals protons sneak through the sodium-potassium pump

Located in the surface membrane of all animals’ cells, sodium-potassium pumps keep cells and the animals that contain them in working order. Among other things, their efforts underlie nerve signals, heart beats and muscle contractions. But as ubiquitous and essential as these pumps are, new research shows scientists have not fully understood how they work.

Research in David Gadsby’s Laboratory of Cardiac/Membrane Physiology has revealed these pumps routinely transport not just sodium and potassium, but also hydrogen ions known as protons.

Pumping protons. A structural rendering of the sodium-potassium pump, which researchers now reveal to be more versatile than previously thought.

Pumping protons. A structural rendering of the sodium-potassium pump, which researchers now reveal to be more versatile than previously thought.

“Scientists have been picking this microscopic machine apart for decades to learn its secrets, and although proton movement through the pump had been glimpsed, it was thought to happen only when the pump was deprived of its normal cargo, sodium and potassium ions,” Gadsby says. “But now we have shown, by very careful measurements, that protons can flow through these pumps under normal conditions.”

Scientists have known for decades the pump moves two potassium ions into the cell for every three sodium ions it transports out. Since cells contain a higher concentration of potassium than is outside the cell, but less sodium than is located outside, this process requires energy. The ions carry an electrical charge, so this movement contributes to an electrical gradient, or a difference in electrical potential, between the inside and outside of the membrane in which the pump is located. These concentration and potential gradients power electrical signals used to send messages or contract muscles within the body.

Working with unfertilized frog eggs, Gadsby and postdoc Natascia Vedovato discovered that under normal conditions, protons, which are positively charged, flow into the cell by hijacking a spot in the pump otherwise reserved for sodium.

Every time a pump goes through a cycle, pushing three sodium ions out and bringing two potassium ions in, there is a chance a proton from outside the cell will find its way into a vacant sodium binding site, and from there, into the cell.

“We do not yet know if this is simply an unavoidable byproduct of the conformation changes that must occur in the pump, or if the proton import is a side job that serves a useful function in some location, at some time, and so has been preserved by evolution,” Gadsby says.

Under normal conditions, the probability that a proton will get in is quite low, but the protons’ chances increase when the environment outside the cell becomes more acidic when more protons are available. The researchers speculate the proton flow might have important implications for cells under certain stressful conditions that create acidic environments, such as in muscle during heavy exercise, in the heart during a heart attack, or in the brain during a stroke.

14march-vosshall Journal of General Physiology 143, 449–464 (March 31, 2014)
Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps
Natascia Vedovato and David C. Gadsby
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