Voltage clamp and tracer flux data: effects of a restricted extra-cellular space

Abstract
In the original Hodgkin & Huxley analysis of the membrane currents in squid giant axon, the time dependence of the currents was attributed to voltage-dependent changes in the permeability of the membrane to the ions involved. According to this theoretical framework, the time constants for the rate of change of current should be unique functions of the membrane potential, and should be independent of the previous history of the voltage and current flowing. In recent years, however, there has been increasing awareness of the fact that, for many physiological preparations, the space just outside the cell membrane is not in good diffusive contact with thebulkextra-cellular fluid perfusing the preparation. Consequently, when current flows across the cell membrane, there are changes in the ion concentrations in this so-called ‘restricted extra-cellular space’ (RECS).