Energy optimisation predicts the capacity of ion buffering in the brain

Neurons store energy in the ionic concentration gradients they build across their cell membrane.The amount of energy stored, and hence the work the ions can do by mixing, can be enhanced by the presence of ion buffers in extra- and intracellular space.Buffers act as sources and sinks of ions, however, and unless the buffering capacities for different ion species obey certain relationships, a complete mixing of the ions may be impeded by the physical conditions of charge neutrality and isotonicity. From these conditions, buffering capacities were calculated that enabled each ion species to mix completely. In all valid buffer distributions the Ca++ ions were buffered most, with a capacity exceeding that of Na+ and K+ buffering by at least an order of magnitude. The similar magnitude of the (oppositely directed) Na+ and K+ gradients made extracellular space behave as a Na+--K+ exchanger. Anions such as Cl- were buffered least.The great capacity of the extra- and intracellular Ca++ buffers caused a large influx of Ca++ ions as is typically observed during energy deprivation.These results explain many characteristics of the physiological buffer distributions but raise the question how the brain controls the capacity of its ion buffers. It is suggested that neurons and glial cells, by their great sensitivity to gradients of charge and osmolarity, respectively, sense deviations from electro-neutral and isotonic mixing, and use these signals to tune the chemical composition, and buffering capacity, of the extra- and intracellular matrices.