Effect of extracellular volume on the energy stored in transmembrane concentration gradients

The amount of energy that can be retrieved from a concentration gradient across a membrane separating two compartments depends on the relative size of the compartments. Having a larger low-concentration compartment is in general beneficial. It is shown here analytically that the retrieved energy further increases when the high-concentration compartment shrinks during the mixing process, and a general formula is derived for the energy when the ratio of transported solvent to solute varies. These calculations are then applied to the interstitial compartment of the brain, which is rich in Na+ and Cl- ions and poor in K+. The reported shrinkage of this compartment, and swelling of the neurons, during oxygen deprivation is shown to enhance the energy recovered from NaCl entering the neurons. The slight loss of energy on the part of K+ can be compensated for by the uptake of K+ ions by glial cells. In conclusion, the present study proposes that the reported fluctuations in the size of the interstitial compartment of the brain (expansion during sleep and contraction during oxygen deprivation) optimize the amount of energy that neurons can store in, and retrieve from, their ionic concentration gradients.