Diuretic therapy has also been shown to reduce myocardial Na, K-ATPase when there is potassium loss. It is also clinically significant in the treatment of atrial fibrillation as it decreases the conduction of the atrioventricular node and causes depression of the sinoatrial node. This physiology is clinically significant in the treatment of heart failure as it increases the contractility of the heart. This positive inotropy stimulates the vagus nerve, causing a decrease in heart rate. This increased intracellular Ca 2+ then increases cardiac contractility. This indirect inhibition of Na+/Ca 2+ exchange, therefore, causes a buildup of Ca 2+ intracellularly because the exchanger cannot allow Ca 2+ to exit the cell since it cannot accept Na+ into the cell. This buildup of intracellular Na+ hinders the concentration gradient that usually drives the Na+/Ca 2+ channel exchanger, which generally pumps Na+ into the cell and Ca 2+ out of the cell because the concentration gradient is not favorable for Na+ to enter the cell as excessive Na+ has built up intracellularly. This inhibition causes a buildup of excessive K+ extracellularly, and accumulation of excessive Na+ intracellularly as the Na+-K+ ATPase can no longer pump K+ into the cell or pump Na+ out of the cell. Other cardiac glycosides such as digoxin and digitoxin directly inhibit the Na+-K+ ATPase. For example, ouabain is a cardiac glycoside that inhibits the Na+-K+ ATPase by binding to the K+ site. One significant clinical application is in cardiovascular pharmacology. Studies show that patients with heart failure have a 40% lower concentration of total Na, K-ATPase. Īs the Na+-K+ ATPase is essential for maintaining various cellular functions, its inhibition could result in diverse pathologic states. Na, K ATPases in the gray matter consumes a significant amount of energy, up to three-quarters of energy is absorbed by Na, K ATPases in the gray matter while merely a quarter of the total energy gets utilized for protein synthesis and molecular synthesis. Astrocytes also need Na, K ATPase pump to maintain the sodium gradient as the sodium gradient maintains neurotransmitter reuptake. Neurons need the Na, K ATPase pump to reverse postsynaptic sodium flux to re-establish the potassium and sodium gradients which are necessary to fire action potentials. The brain also requires NA, K ATPase activity. Sperm needs the Na, K ATPase to regulate membrane potential and ions, which is necessary for sperm motility and the sperm’s acrosome functioning during penetration into the egg. Sperm cells also use the Na, K-ATPase, but they use a different isoform necessary for preserving fertility in males. This sodium gradient is necessary for the kidney to filter waste products in the blood, reabsorb amino acids, reabsorb glucose, regulate electrolyte levels in the blood, and to maintain pH. The kidneys have a high level of expression of the Na, K-ATPase, with the distal convoluted tubule expressing up to 50 million pumps per cell. Sodium and potassium gradients function in various organ systems' physiologic processes. Na, K-ATPase is a crucial scaffolding protein that can interact with signaling proteins such as protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K). Furthermore, the physiologic consequences of inhibiting the Na+-K+ ATPase are useful and the target in many pharmacologic applications. It plays a crucial role on other physiological processes, such as maintenance of filtering waste products in the nephrons (kidneys), sperm motility, and production of the neuronal action potential. The sustained concentration gradient is crucial for physiological processes in many organs and has an ongoing role in stabilizing the resting membrane potential of the cell, regulating the cell volume, and cell signal transduction. The sodium and potassium move against the concentration gradients. The Na+ K+-ATPase pump maintains the gradient of a higher concentration of sodium extracellularly and a higher level of potassium intracellularly. The Na+K+-ATPase pump helps to maintain osmotic equilibrium and membrane potential in cells. The plasma membrane is a lipid bilayer that arranged asymmetrically, containing cholesterol, phospholipids, glycolipids, sphingolipid, and proteins within the membrane. The Na+ K+ ATPase pumps 3 Na+ out of the cell and 2K+ that into the cell, for every single ATP consumed. The Na+ K+ pump is an electrogenic transmembrane ATPase first discovered in 1957 and situated in the outer plasma membrane of the cells on the cytosolic side.
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