Explain the mechanisms responsible for the cell resting membrane potential (60% of marks) and describe the Gibbs Donnan effect (40% of marks)
A good answer included a definition of the resting membrane potential and a clear description of
the factors that determine it. Explanation of these factors should have included a detailed
description of the selective permeability of the membrane, electrochemical gradients and active
transport mechanisms. Answers should demonstrate awareness of the Nernst equation and the
Goldman-Hodgkin-Katz equation. These were often confused, sometimes with the GibbsDonnan
effect. Descriptions of the Gibbs-Donnan effect generally lacked detail and
understanding. The better answers included a definition and discussed in detail the influence of
non-diffusible ions (intracellular proteins) on the distribution of diffusible ions.
This is a topic which generally takes an entire book chapter to describe. What follows is an attempt to explain/describe the main concepts as briefly as possible while including the essential details.
Resting membrane potential: the voltage (charge) difference between the intracellular and extracellular fluid, when the cell is at rest (i.e not depolarised by an action potential).
Mechanisms responsible for the resting membrane potential:
- Chemical gradients generated by active transport pumps: the concentration of ions are significantly different between the intracellular and extracellular fluid, eg. the ratio of potassium ions is 35:1.
- Selective membrane permeability: the cell membrane is selectively ion-permeable, specifically it is much more permeable to potassium ions
- Electrical gradients are generated because potassium leak (via K2P channels) from the intracellular fluid creates a negative intracellular charge. This charge attracts potassium ions back into the cell and thus opposes the chemical gradient.
- Electrochemical equilibrium develops when electrical and chemical forces are in balance for each specific ion species, and this is described by the Nernst equation.
- The Nernst potential for each ion is the transmembrane potential difference generated when that ion is at electrochemical equilibrium
- The total membrane resting potential for all important ion species is described by the Goldman-Hodgkin-Katz equation, which takes into account the different membrane permeabilities for each ion.
- At rest, with normal intracellular and extracellular electrolyte concentrations, the net charge of the intracellular side of the cell membrane is negative, and is approximately -70 to -90 mV for mammalian neurons.
Now, as for the Gibbs-Donnan effect:
- The Gibbs-Donnan effect describes the unequal distribution of permeant charged ions on either side of a semipermeable membrane which occurs in the presence of impermeant charged ions.
- At Gibbs-Donnan equilibrium,
- On each side of the membrane, each solution will be electrically neutral
- The product of diffusible ions on one side of the membrane will be equal to the product of diffusible ions on the other side of the membrane
- The electrochemical gradients produced by unequal distribution of charged ions produces a transmembrane potential difference which can be calculated using the Nernst equation
- The presence of impermeant ions on one side of the membrane creates an osmotic diffusion gradident attracting water into that compartment.
- The mechanisms which maintain the resting membrane potential and the mechanisms of the Gibbs-Donnan effect are different phenomena:
- The Donnan equlibrium is a completely passive process: i.e. no active transporters are involved in maintaining this equilibrium.
- A Donnan equilibrium is an equilibrium, i.e. ion concentrations on either side of the barrier are static.
- If the Donnan equilibrium were to become fully established, the increase in intracellular ions would cause cells to swell due to the osmotic influx of water.
- At a Donnan equilibrium, the resting membrane potential would be only about -20 mV. This potential would exist even if the membrane permeability for all ions was the same.
- The resting membrane potential, in contrast, requires different permeabilities for potassium and for sodium, and is maintained actively by constant Na+/K+ ATPase activity.
- Because biological membranes (especially of exciteable tissues) are never at equilibrium, the Goldman-Hodgkin-Katz equation is usually a better choice for explaining their electrochemical behaviour.
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