L2.2 ATP-DEPENDENT ION PUMPS AND ION EXCHANGERS PDF

Membrane and receptors module Session 2 Lecture 2. 2 ATP-DEPENDENT ION PUMPS AND ION EXCHANGERS Dr. Ahmed Faisal Obed Aims To outline the major physiological roles of Sodium-potassium ATPase (Na+-K+-ATPase, Na pump) Plasma membrane Ca2+ ATPa...

Membrane and receptors module Session 2 Lecture 2. 2 ATP-DEPENDENT ION PUMPS AND ION EXCHANGERS Dr. Ahmed Faisal Obed Aims To outline the major physiological roles of Sodium-potassium ATPase (Na+-K+-ATPase, Na pump) Plasma membrane Ca2+ ATPase (PMCA) Sarco(endo)plasmic reticulum ATPase (SERCA) Sodium calcium exchange (NCX) Sodium hydrogen exchange (NHE) Anion exchange (AE)  To consider how ion transporters work together in cell physiology To consider how ion transport contributes to Cellular Ca2+ handling Cellular pH regulation Cell volume regulation Renal bicarbonate reabsorption  Na+-K+-ATPase (Na pump) Forms Na+ and K+ gradients in resting cell Drives many secondary active transport processes – Ion homeostasis, [Ca2+], pH, cell volume, resting membrane potential, nutrient uptake. Control of intracellular Ca2 + Sodium calcium exchanger (NCX) It uses the energy from influx of Na+ down its electrochemical gradient exchanges 3 Na+ for 1 Ca2+. Low affinity High capacity * NCX activity is membrane potential dependent * In depolarised cells, the normal mode of operation of NCX is inhibited and its mode of operation reverses. So NCX makes a contribution to Ca2+ influx during the cardiac action potential. Sodium Calcium Exchanger (NCX) in Ischemia - Na+-K+ ATPase pump inhibited - NCX reversed - [Na+]in exchanges for [Ca2+]out - High [Ca2+] contributed to toxicity during ischemia. Plasma Membrane Ca2+ ATPase (PMCA) It has a much higher affinity but a much lower capacity. So it is responsible for maintaining the very low concentrations of calcium that are normally found within a cell. Therefore the activities of the NCX and the PMCA complement each other.  Sarco/endoplasmic reticulum Ca2+ - ATPase (SERCA) SERCA resides in the sarcoplasmic reticulum (SR) within muscle cells. It is a Ca2+ ATPase that transfers Ca2+ from the cytosol of the cell to the lumen of the SR at the expense of ATP hydrolysis during muscle relaxation.  Ion transporters in cellular pH regulation Cellular pH is controlled by the activity of membrane transporters In cellular acidosis there will be expelling of H+ or entering of HCO3- into the cell In alkalosis is apposed by expelling of HCO3- via the anion exchanger. Na/K pump again drives other channels, by keeping intracellular Na+ concentration low, so NHE can pump H+ ions into the proximal tubule lumen. H+ goes into the lumen to “pick up” bicarbonate and bring it back into the cell.  The goal of Renal anti-hypertensive therapy is to reduce the reuptake of Na+ and other molecules, so less water is reabsorbed via.osmosis Block of one or more of the Na+ reabsorption mechanisms with diuretic drugs can be used to increase Na+ excretion to produce a hyperosmotic urine and, hence, the excretion of water. This is the principle of treatment of oedema and hypertension