The sodium–potassium pump is a transmembrane protein that is firmly anchored in the cell membrane. With the help of this protein, sodium ions can be transported out of the cell and potassium ions into the cell.
What is the sodium-potassium pump?
The sodium–potassium pump is a pump located in the cell membrane. It maintains the so-called resting membrane potential by transporting sodium and potassium ions. In each pump cycle, it exchanges three sodium ions (Na+ ions) for two potassium ions (K+ ions). In this way, it provides a negative potential in the intracellular space. In transporting these ions, the sodium-potassium pump consumes energy in the form of adenosine triphosphate (ATP).
Function, action, and roles
The sodium-potassium pump functions primarily as a carrier protein. It has three binding sites for sodium ions and two binding sites for potassium ions. Similarly, there is also one binding site for ATP. Consuming ATP, the ion pump can transport three sodium ions from the cytoplasm into the extracellular space. In return, it transports two potassium ions from the cytoplasm into the cell. This process occurs in several steps. First, the carrier protein is open to the cytoplasm. Three sodium ions enter the protein through the opening and bind to the specific binding sites. On the inside of the protein membrane, an ATP molecule also attaches to the designated binding site. This molecule is then cleaved with the release of water. A resulting phosphate group is bound for a short time by an amino acid of the sodium-potassium pump. Energy is released during the cleavage of the ATP molecule. This changes the spatial arrangement of the sodium-potassium pump and the carrier protein opens toward the extracellular space. The three sodium ions then detach from their binding sites and enter the external medium. Two potassium ions now enter the protein through the open gap. These also attach themselves to the binding sites. The bound phosphate group is now cleaved off. This changes the conformation of the sodium-potassium pump back to its original state. Now the potassium ions detach and flow into the cell interior. Through this process, the sodium-potassium pump maintains the so-called resting membrane potential.
Formation, occurrence, and properties
Resting membrane potential refers to the membrane potential of potentially excitable cells at rest. Membrane potentials are found particularly in nerve cells or in muscle cells. Depending on the cell type, the resting membrane potential ranges from -100 to -50 mV. In most nerve cells it is -70 mV. Thus, the cell interior is negatively charged compared to the cell exterior. The resting potential of a cell is a prerequisite for the excitation conduction of nerves and for the control of muscle contraction. The sodium-potassium pump can be inhibited by various substances. For example, cardiac glycosides inhibit the carrier protein. Cardiac glycosides are prescribed for chronic heart failure and atrial fibrillation. By inhibiting the pump, more sodium remains in the cells. The intracellular sodium concentration and the extracellular sodium concentration converge. Inhibition of the sodium-calcium exchanger causes more calcium to remain in the cell. This increases the contractility of the heart. However, inhibition of the sodium-potassium pump can also lead to hyperkalemia. Conversely, pharmacologically, the sodium-potassium pump can also be stimulated. This is done, for example, by administering insulin or epinephrine. Stimulation of the pump may lead to hypokalemia.
Diseases and disorders
A very rare disorder underlying a defect in the sodium-potassium pump is acute-onset parkinsonism-dystonia syndrome. It is a disorder that is inherited in an autosomal dominant manner. It usually begins in childhood or adolescence. Within hours, dystonia occurs with tremors, spasms, and involuntary movements. After a short time, this is followed by a high-grade lack of movement and even immobility. An effective therapy for the disease is not yet known. Some animal studies suggest that defects in the sodium-potassium pump may be a possible cause of epilepsy. In the search for gene defects that could cause epilepsy, researchers came across a mutation in the ATP1a3 gene.This is responsible for the function of the sodium-potassium pump. Epilepsy is also known in German as Krampfleiden or Fallsucht. Depending on the region of the brain that discharges in the seizure, different symptoms occur. For example, twitching or tensing of the muscles may occur, the affected person may make loud seizure-like noises, or they may perceive flashes, streaks or shadows. Unpleasant smell misperceptions or acoustic perception disturbances can also occur. In particular, the so-called status epilepticus can become life-threatening. These are generalized tonic-clonic seizures that can last between 5 and 30 minutes. A defect in the sodium-potassium pump could also be a possible trigger of migraine. Researchers have discovered gene alterations on chromosome 1 in migraine patients. This gene leads to a defect in the sodium-potassium pump in the membranes of the cells. As a result, distended and rounded cells develop. This is believed to cause the characteristic pain of migraine. Migraine is a neurological disease affecting about 10% of the population. Women are affected significantly more often than men. The clinical picture of migraine is very variable. Typically, it comes to attack-like, pulsating and hemiplegic headaches. These recur periodically. In addition, symptoms such as nausea, vomiting, sensitivity to sound or light may also occur. Some patients report visual or sensory disturbances of perception before the actual migraine attack. This is also referred to as migraine aura. Migraine is a diagnosis of exclusion and currently has no cure.
