Transport Across Cell Membranes

Explain mechanisms of transport of substances across cell membranes, including an understanding of the Gibbs-Donnan effect.

Substances can cross cell membranes by diffusion, active transport, and exo- or endocytosis.

Diffusion

There are several types of diffusion:

• Simple diffusion
  Molecules pass through the cell membrane or via a channel. This process is passive, and occurs down a concentration gradient.
  • Only lipid soluble molecules (gases, steroids) can pass directly through the lipid bilayer without a specialised channel
  • Voltage-gated and ligand-gated channels facilitate simple diffusion

• Facilitated diffusion (uniporters)
  Molecules bind to a carrier protein, and move together through the lipid bilayer, before separating on the other side. Facilitated diffusion is concentration gradient-dependent, and limited by the amount of carrier protein available..

The rate and extent of diffusion is affected by:

• Hydrostatic pressure gradients
• Concentration gradients
• Electrical gradients

Active Transport

Substances that are moved against a concentration gradient require active transport, and requires energy in the form of ATP. Active transport mechanisms may be:

• Primary active transport
  The substance itself is moved.
• Secondary active transport
  The substance moves against a concentration gradient with another molecule that had a gradient established by active transport.
  • This molecule is typically sodium

• Co-transporters (symporters)
  Uses carrier proteins and moves two substances (e.g. sodium and an amino acid) across a membrane.
  • This process will be passive if the energy gained moving one substance down its concentration gradient is greater than the energy required to move the other substance up its concentration gradient
• Counter-transporters (antiporters)
  Use carrier proteins and moves two substances in opposite directions across the membrane.
  • May be active or passive

Key transporters include:

• The Na⁺-K⁺ ATP-ase pump
  This moves three sodium ions out of a cell and two potassium ions in, cleaving one ATP in the process. This pump has many functions:
  • Maintenance of cellular volume (which would otherwise burst from the influx of water with changing ECF tonicities) by net loss of osmoles
  • Maintenance of the potential difference across the membrane
  • Establishment of chemical gradients to be used in secondary active transport mechanism
    • e.g. Reabsorption of glucose in the kidney via the S-GLUT transporter

Exo- and Endocytosis

These processes describe the formation of a vesicle (typically from membrane phospholipid) to transport substances:

• Exocytosis
  Vesicle containing a substance to be secreted fuses with the cell membrane when activated by calcium, depositing the substance outside the cell.

• Endocytosis
  The cell membrane invaginates around the substance, absorbing the substance into the cell. A vesicle (or vacuole) may or may not be created. Endocytosis may be subdivided into:
  • Phagocytosis, where leukocytes engulf bacteria into a vacuole
  • Pinocytosis, where substances are endocytosed but not into a vacuole

Gibbs-Donnan Effect

Describes the tendency of diffusable ions to distribute themselves such that the ratios of the concentrations are equal when they are in the presence of non-diffusable ions.

The Gibbs-Donnan Effect:

• Occurs when:
  • A semi-permeable membrane separates two solutions
  • At least one of those solutions contains a non-diffusable ion
• The distribution of permeable charged ions will be influenced by both their valence and the distribution of non-diffusable ions, such that at equilibrium the products of the concentrations of paired ions on each side of the membrane will be equal:
  $[Na^+]_A \times [Cl^-]_A = [Na^+]_B \times [Cl^-]_B$
• Alters tonicity on either side of the cell membrane, causing movement of water which then upsets the Gibbs-Donnan effect
  This results in no 'steady' stable state.

The two main contributors to the Gibbs-Donnan effect in the body are sodium and protein. This occurs because cell membranes:

• Are impermeable to protein
  Intracellular protein concentration is high.
• Effectively impermeable to sodium
  Due to the Na⁺-K⁺ ATP-ase pump.

Changing Gibbs-Donnan equilibriums also change the tonicity on each side of the cell membrane, causing movement of water which then upsets the Gibbs-Donnan effect - therefore there is no stable state.

The Gibbs-Donnan Effect is important for:

• Maintenance of cell volume
  Na⁺ acts as an effective osmole, reducing cellular swelling.
• Plasma oncotic pressure
  Increased plasma ion concentration increases oncotic pressure.
• Resting Membrane Potential

References

1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.
2. Eaton DC, Pooler JP. Vander's Renal Physiology. 6th Ed (Revised). McGraw-Hill Education - Europe. 2004.