Membrane and Receptors Module - Lecture 2.2

Membrane and Receptors Module - Session 2, Lecture 2.2

• ATP-Dependent Ion Pumps and Ion Exchangers
• Aims:
  • Outline the physiological roles of sodium-potassium ATPase (Na⁺-K⁺-ATPase), plasma membrane Ca²⁺ ATPase (PMCA), sarco(endo)plasmic reticulum ATPase (SERCA), sodium calcium exchange (NCX), sodium hydrogen exchange (NHE), and anion exchange (AE).
  • Explain how ion transporters work together in cell physiology.
  • Show how ion transport contributes to cellular Ca²⁺ handling, cellular pH regulation, cell volume regulation, and renal bicarbonate reabsorption.

Sodium-Potassium ATPase (Na⁺-K⁺-ATPase)

• Forms Na⁺ and K⁺ gradients in resting cells.
• Drives secondary active transport processes.
• Important for ion homeostasis, Ca²⁺ regulation, pH balance, cell volume, resting membrane potential, and nutrient uptake.

Control of Intracellular Ca²⁺

• Resting [Ca²⁺]:
  • Regarded as low, mainly maintained at <100 nm.
  • Achieved in conjunction with plasma membrane Ca²⁺-ATPase (PMCA) and Na⁺-Ca²⁺ exchanger (NCX) maintaining gradients and removal mechanisms.
  • Plays a significant role in transporting Ca⁺² across membranes.
  • Sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA) is responsible for actively pumping Ca²⁺ from the cytosol into these cellular compartments.
• Na⁺-Ca²⁺ exchanger (NCX):
  • Uses the energy of Na⁺ influx down its electrochemical gradient to exchange 3 Na⁺ for 1 Ca²⁺.
  • Low affinity but high capacity.
  • Its activity is potential dependent.
  • In depolarised cells, the normal mode of operation is inhibited and reverses.
  • Makes a contribution to Ca²⁺ influx during the cardiac action potential.

Sodium Calcium Exchanger (NCX)

• Uses the energy from Na⁺ influx down its electrochemical gradient.
• Exchanges 3 Na⁺ for 1 Ca²⁺.
• Exhibits low affinity and high capacity.
• Its activity is membrane potential dependent.
• In polarised cells, it maintains low intracellular Ca²⁺ concentration.
• In depolarised cells, it contributes to Ca²⁺ influx, as the mode of operation reverses.

Plasma Membrane Ca²⁺-ATPase (PMCA)

• High affinity but low capacity.
• Responsible for maintaining very low intracellular Ca²⁺ concentrations.
• Complements the actions of the NCX.

Sarco/Endoplasmic Reticulum Ca²⁺-ATPase (SERCA)

• Located in the sarcoplasmic reticulum (SR).
• Pumps Ca²⁺ from the cytosol to the SR lumen during muscle relaxation, using ATP hydrolysis.

Ion Transporters in Cellular pH Regulation

• Cellular pH is controlled by membrane transporters.
• In acidosis, H⁺ is expelled and/or HCO₃⁻ enters the cells.
• In alkalosis, HCO₃⁻ is expelled via the anion exchanger.

Bicarbonate Reabsorption by the Proximal Tubule

• The kidneys reabsorb all the filtered bicarbonate to retain base for maintaining pH.
• This process involves the sodium-hydrogen exchanger (NHE) and carbonic anhydrase.

Na⁺/K⁺ Pump

• Plays a role in maintaining low intracellular Na⁺ concentration, facilitating H⁺ pumping into the proximal tubule lumen by NHE.
• Allows H⁺ to "pick up" bicarbonate and bring it back into the cell.

Renal Anti-hypertensive Therapy

• Reduces Na⁺ and other molecule reuptake by kidneys to lower water reabsorption via osmosis.

Diuretic Drugs

• Block one or more Na⁺ reabsorption mechanisms to increase Na⁺ excretion and water excretion.
• The principle of oedema and hypertension treatment.

Explore the physiological roles of key ion pumps such as Na⁺-K⁺-ATPase and PMCA in cellular processes. This quiz delves into how these transporters work together to regulate calcium handling, pH balance, and volume control. Understand the foundational concepts behind membrane physiology and ion transport mechanisms.