111' StructureFunction of the Plasma Membrane

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11-1. Structure/Function of the Plasma Membrane
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Movement of Substances across Cell Membranes

• Plasma membrane dual function
• Retain dissolved materials
• Allow exchange of materials
• Two means of movement
• Passive
• Active via energy-coupled transport processes
• Both lead to a net flux of an ion or compound
• Influx and Efflux are not balanced

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Movement of Substances across Cell Membranes

• Four processes are known
• Simple diffusion through lipid bi-layer
• Simple diffusion through aqueous, protein-lined
  channels
• Facilitated diffusion
• Active transport

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Movement of Substances across Cell Membranes

• Energetics of solute movement
• Uncharged may move via diffusion gradient
• Charged two gradients
• Chemical gradient
• Electrical potential gradient
• Together form an electrochemical gradient

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Movement of Substances across Cell Membranes
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Movement of Substances across Cell Membranes

• Diffusion through membranes
• Rate dependent on polarity and size
• Polarity estimated using the partition
  coefficient
• The greater the lipid solubility the faster the
  rate of diffusion
• Smaller molecules penetrate more rapidly than
  (similar) larger molecules
• Highly permeable to O2, CO2, NO and H2O

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Movement of Substances across Cell Membranes

• Diffusion through membranes
• Large polar molecules sugars, aa,
  phosphorylated intermediates poor permeability
• These are essential for cell function must be
  actively transported

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Movement of Substances across Cell Membranes

• Diffusion of Water
• Water moves much more rapidly through the
  membrane than solutes
• Membrane is termed semi-permeable
• Movement of water is termed osmosis

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Movement of Substances across Cell Membranes

• Diffusion of Water
• A compartment with high solute concentration
  hypertonic
• A compartment with low solute concentration -
  hypotonic

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Movement of Substances across Cell Membranes

• Diffusion of Ions through Membranes
• Plasma membrane is highly impermeable to
• Na, K, Ca2 and Cl-
• But their conductance is critical
• Ion Channels provide the mechanism for their
  transport

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Movement of Substances across Cell Membranes

• Diffusion of Ions through Membranes
• The patch-clamp technique of Sakmann and Neher

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Movement of Substances across Cell Membranes

• Diffusion of Ions through Membranes
• Most channels exist in an open or closed
  conformation
• Term gated two categories
• Voltage-gated channels
• Ligand-gated channels

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Movement of Substances across Cell Membranes

• Diffusion of Ions through Membranes
• Voltage-gated channels K channels
• All have similar molecular architecture
• N- and C- terminals on cytoplasmic side
• Six membrane-spanning domains S1-S6
• A single channel consists of four identical
  polypeptide subunits
• Subunits arranged symmetrically around
  ion-conducting pore

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Movement of Substances across Cell Membranes

• Diffusion of Ions through Membranes
• Voltage-gated channels K channels
• Between S5 and S6 segment H5 (also termed P)
  dips into the center and forms the pore (4
  polypeptides)

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Movement of Substances across Cell Membranes

• Diffusion of Ions through Membranes
• Voltage-gated channels K channels
• P region contains conserved pentapeptide
  Thr-Val-Gly-Tyr-Gly
• Termed the selectivity filter

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Movement of Substances across Cell Membranes

• Diffusion of Ions through Membranes
• Voltage-gated channels K channels
• S4 contains multiple ve charged aa which act as
  voltage sensors

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Movement of Substances across Cell Membranes

• Facilitated Diffusion
• Many examples of diffusing substrates which
  selectively bind to a membrane-spanning protein-
  a facilitative transporter
• Mediate solute movement in both directions
• Dependent on concentration gradient
• Example glucose transporter

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Movement of Substances across Cell Membranes

• Facilitated Diffusion
• Glucose transporter
• Continued transport achieved by phosphorylating
  glucose and maintaining the glucose gradient
• Glut 4 is the insulin-responsive glucose
  transporter

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Movement of Substances across Cell Membranes

• Active Transport
• Typical specific ion concentration gradients are
  very steep
• For cells to develop such steep gradients
  requires active transport
• Requires coupling of energy
• Hydrolysis of ATP
• Active transport proteins termed pumps

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Movement of Substances across Cell Membranes

• Active Transport
• Enzyme driven
• Na/KATP-ase termed sodium-potassium pump
• Drives the transport of ions in one direction
• For each ATP hydrolysed
• Three Na pumped out
• Two K pumped in

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Movement of Substances across Cell Membranes

• Active Transport - sodium-potassium pump
• Conformational changes in the protein change its
  affinity for the ions
• Achieved by phosphorylation of the protein
• Consider its importance!!!!
• Consumes approx 1/3 of the energy of most animal
  cells (2/3 the energy of nerve cells)

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Movement of Substances across Cell Membranes

• Active Transport - sodium-potassium pump