Updated: 6/17/2018

Plasma Membrane

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Overview
  • 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
  • Function
    • selective permeability
      • controls an intracellular environment distinct from extracellular environment
    • signalling
    • localization of enzymes to promote or inhibit interaction
Membrane Physiology
  • 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
          • Ex+ = 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 (Emem)
    • 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-
            • Emem = Gx(Ex+) + Gy(Ey+) + Gz(Ez-)
        • 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 Emem = Ex+ , there is no net movement of ions and net force = 0
    • example
      • Emem = -77 mV
      • EK+ = -95 mV
      • is diffusion of K+ across this membrane favorable?
        • Yes, given open channels (G) to K+ it will diffuse until Emem = -95 mV
    • inside cells (as compared to extracellular environment)
      • ↑ K+
        • EK+ = -95 mV
        • G is high for K+→ changes in [K+]extracellular will have a large impact on Emem
          • hyper/hypokalemia very dangerous clinically
        • ↑ G will hyperpolarize cell
          • efflux from cell
      • ↓ Na+
        • ENa+ = +45 mV
        • G is low for Na+ → changes in [Na+]extracellular will NOT have a large impact on Emem
        • ↑ G will depolarize cell
          • influx into cell
      • ↓ Cl-
        • ECl- = -90 mV
        • since in most cells Emem = -90 mV → Cl- is at equilibrium and will not diffuse

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