Plasma Membrane

Introduction – Plasma Membrane

The plasma membrane, also known as the cell membrane, is a thin, semi-permeable layer that surrounds all living cells. It separates the inside of the cell from the outside environment and controls the exchange of materials between the cell and its surroundings.

Overview – Plasma Membrane

• Structure 
  • bilayer of phospholipids
  • asymmetrical in respect to intracellular and extracellular faces
  • “fluid mosaic”
  • composition
    • cholesterol
      • ~50%
      • adds thermal stability to membrane
        • i.e. ↑ melting temperature
      • ↓ membrane flexibility
      • amount in plasma membrane tightly regulated
    • phospholipids
      • ~50%
    • sphingolipids
      • fatty acid chain attached to a sphingosine
      • disorders of sphingolipid metabolism
        • Fabry’s disease
        • Gaucher’s disease
        • see Lysosome topic 
    • glycolipids
    • proteins
      • pumps
        • move substances against their concentration gradient
        • requires energy
        • e.g. Na⁺-K⁺ ATPase
          • transmembrane pump
          • ATP binding-site accessible from cytoplasm
          • process
            • 3 Na⁺ bind pump intracellularly
            • ATP binds and phosphorylates the pump
            • pump changes conformation which releases 3 Na⁺ extracellularly
            • 2 K⁺ bind pump extracellularly
            • phosphate ion removed
            • pump changes conformation which releases 2 K⁺ intracellularly
            • 3 Na⁺ bind pump intracellularly (repeat)
            • net: each ATP results in 3 Na⁺ out and 2 K⁺ in
          • pharmacological importance
            • cardiac glycosides (digoxin and digitoxin)
              • mechanism of action
                • inhibits pump
                • depolarization of cell membrane
                • ↑ intracellular [Na⁺]
                • ↓ Na⁺ gradient required for Na⁺/Ca²⁺ exchange
                • ↑ [Ca²⁺] intracellularly
                • ↑ cardiac contractility
            • ouabain
              • inhibits by binding to K⁺ site
              • similar response to cardiac glycosides
      • channels
        • move substances down their concentration gradient
        • 3 types
          • ungated
            • always open
            • e.g. K⁺-channel
          • voltage-gated
            • open in response to changes in membrane voltage
            • e.g. found in excitable tissue
          • ligand-gated
            • open in response to a ligand
            • e.g. post-synaptic membrane receptors

Function – Plasma Membrane

• Function
  • selective permeability
    • controls an intracellular environment distinct from extracellular environment
  • signalling
  • localization of enzymes to promote or inhibit interaction

Membrane Physiology – Plasma Membrane

• Electrochemical potential
  • determined by
    • conductance (G)
      • ability of ions to move across a membrane
      • controlled by opening and closing channels
        • ↑ channels = ↑ conductance
    • net force
      • combination of
        • concentration force
          • concentration difference of a substance across a membrane
        • electrostatic force
          • attraction of unlike charges
          • repulsion of like charges
• Equilibrium potential
  • defined as the electrical potential across a membrane that would prevent the diffusion of a substance via its concentration force for a given concentration difference across a membrane
  • measured in millivolts (mV)
  • for a single substance
    • calculated by
      • Nernst equation
        • E_x+ = 60/Z log( [X⁺]_extracell / [X⁺]_intracell )
          • Z = absolute value of ionic charge
            • K+, Cl-, Na+ = 1, Ca²⁺ = 2
          • Answers the question: what is the voltage that exists across a membrane when a certain ion is at its equilibrium
            • Another way of thinking of this: what is the voltage required so that there will be no net flow of a certain ion?
            • For example: -80 mV is the Nernst potential for potassium
              • this means that if the inside of the cell was -80 mV, K+ would not leave or enter the cell
              • The -80 mV of the cell pulling K+ in is equal to the concentration gradient that wants to pull K+ out (remember that K+ is low outside the cell and wants to travel down its ion gradient)
              • If the voltage became -81 mV then K+ would want to travel into the cell as this negative charge would overpower the drive for K+ to travel down its concentration gradient out of the cell
              • If the voltage was -79 mV then K+ would leave the cell as the concentration gradient pulling K+ out is greater than the negative voltage attracting/holding K+ in
  • does NOT determine rate of ionic diffusion → only whether diffusion is favorable
• Resting membrane potential (E_mem)
  • equilibrium potential of most cells = -90 mV
    • calculated by
      • sum of individual membrane potentials for all permeable ions proportional to their conductances
        • for ions X⁺, Y⁺, and Z^–
          • E_mem = G_x(E_x+) + G_y(E_y+) + G_z(E_z-)
      • note: the closer the resting membrane potential is to the equillibrium potential of an individual ion, the greater the membrane conductance is for that ion
        • when E_mem = E_x+ , there is no net movement of ions and net force = 0
  • example
    • E_mem = -77 mV
    • E_K+ = -95 mV
    • is diffusion of K⁺ across this membrane favorable?
      • Yes, given open channels (G) to K⁺ it will diffuse until E_mem = -95 mV
  • inside cells (as compared to extracellular environment)
    • ↑ K⁺
      • E_K+ = -95 mV
      • G is high for K⁺→ changes in [K⁺]_{extracellular} will have a large impact on E_mem
        • hyper/hypokalemia very dangerous clinically
      • ↑ G will hyperpolarize cell
        • efflux from cell
    • ↓ Na⁺
      • E_Na+ = +45 mV
      • G is low for Na⁺ → changes in [Na⁺]_{extracellular} will NOT have a large impact on E_mem
      • ↑ G will depolarize cell
        • influx into cell
    • ↓ Cl^–
      • E_Cl– = -90 mV
      • since in most cells E_mem = -90 mV → Cl^– is at equilibrium and will

Complications

• Permeability changes: The permeability of the plasma membrane is critical for regulating the movement of substances in and out of the cell.
• Membrane damage: The plasma membrane can be damaged by physical or chemical stress, including extreme temperatures, mechanical disruption, and exposure to toxins.
• Receptor dysfunction: Many important cellular processes rely on the interaction of signaling molecules with specific receptors on the plasma membrane.
• Alterations in membrane fluidity: Changes in the composition or structure of membrane lipids, or exposure to environmental factors, can alter membrane fluidity and impact cellular processes.
• Membrane-bound protein dysfunction: Many important proteins, including enzymes and transporters, are embedded in the plasma membrane.

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