Membrane Channels and Pumps

Diffusion

• diffusion: net movement from high to low concentration and ultimate uniform distribution over time

• impacted by:

  • temperature, viscosity, molecular size and mass, distance

  • membrane permeability!!

Diffusion across Biological Membrane

• same principles as simple diffusion for molecules that can easily pass through the lipid bilayer

  • ex: oxygen diffusion into and out of the bloodstream

Diffusion & Membrane Permeability

• small nonpolar - simple diffusion - high permeability = crosses easily

  • ex: O₂, CO₂

• small uncharged polar molecule - slow diffusion (via channels) - low permeability = slower, variable

  • ex: ethanol, H₂O

• larger polar molecules - facilitated diffusion via carriers - very low permeability = requires proteins

  • ex: glucose

• charged molecules - channels or active transport - impermeable otherwise

  • ex: amino acids, ions

Active and Passive Transport

• lipophilic molecules can pass through cell membranes because they dissolve in the lipid bilayer

• simple diffusion: process which lipophilic molecules move across membrane, down the conc. gradient, from high to low concentration

Active Transport

• active transport: process which molecules are transported across the membrane, against the conc. gradient, with the input of energy from another source

• solutes that require active transport are too large and/or polar for simple diffusion

• each membrane transporter has its own unique activity:

  • specificity, saturation, competition, inhibition, etc.

• positive ∆G = needs energy to occur

  • the higher the conc. ratio, the higher the energy cost to maintain

Examples

• primary transport

• secondary transport

• exocytosis

• endocytosis

Membrane Transporter Proteins

• 3 main classes of active transporters:

  • pumps: catalyze active transport of ions against their electrochemical gradient

    • ex: Na⁺/K⁺ ATPase (pump) = enzyme that hydrolyzes ATP to generate sodium and potassium gradients across the membrane

      • hydrolysis of ATP only occurs when sodium and potassium are present

      • requires Mg²⁺

      • 3 sodium and 2 potassium ions are transported per catalytic cycle

        • inside of the cell more negative compared to the outside → electrochemical gradient generated

      • digoxin = N⁺/K⁺ inhibitor

        • blocks dephosphorylation of E2-P form of the ATPase when applied extracellularly

        • decreases in the Na⁺ gradient = slower removal of Ca²⁺ → increase in cellular Ca²⁺ enhances contractile ability of the heart

      • multidrug resistance: development of resistance to once drug makes the cells less sensitive to a range of other compounds

        • MDR protein: acts as an ATP-dependent pump that efflues a range of small molecules including drugs

    • ex: P-Type ATPases = family of ATPases that form phosphorylated aspartate intermediate

      • ex: gastric H⁺-K⁺ ATPase = pumps protons into the stomach to lower the pH

    • exist in 2 conformations:

      • ion binding site facing into the cell

      • ion binding site facing out of the cell

      • ∆G of ATP hydrolysis is coupled with the interconversion of the conformations to pump ions across a membrane

  • carriers

    • antiporters = secondary transporters that transport substrates in opposite directions

    • symporters = secondary transporters that transport substrates in the same direction

    • uniporters = carriers that transport a substrate in either direction based solely on species concentrations

  • channels

Passive Transport

• passive transport: process which molecules are transported across the membrane, down the conc. gradient, without using cellular energy

• negative ∆G = produces energy

• ion channels: allow for the rapid movement of ions across membranes

  • rates approach the rates expected for ions diffusing freely through aqueous solutions

  • interior of neuronal cells contains a high conc. of potassium and low conc. of sodium

    • generated by Na/K pump

    • cation gradient is exploited as an action potential

Examples

• simple diffusion: process which lipophilic molecules move across membrane, down the conc. gradient, from high to low concentration

• facilitated diffusion: process which polar molecules are transported across the membrane, down the conc. gradient by a specific channel

  • considered passive transport because the driving energy of ion movement comes from the ion gradient itself

• osmosis

• bulk flow

• filtration

Specific Channels can Rapidly Transport Ions

• ion channels: allow for the rapid movement of ions across membranes

  • rates approach the rates expected for ions diffusing freely through aqueous solutions

  • interior of neuronal cells contains a high conc. of potassium and low conc. of sodium

    • generated by Na/K pump

    • cation gradient is exploited as an action potential