Electrochemical Information Transfer at Cell Surfaces and Junctions — Application to the Study and Manipulation of Cell Regulation

Abstract

There is now little doubt that low level pulsating current can modulate in vitro and in vivo cell behaviour. One major clinical application of this is the repair of some recalcitrant bone fractures. Guided by the historical speculation that electrical currents were in some way associated with all cell and tissue regulation and/or activity, a working hypothesis was established to provide an electrochemical basis for the possibility of kinetic modulation of cell function. To this end a kinetic analysis was performed of the possible modes by which a real time cellular response to low level pulsating current could occur. Verification of this in some cell systems appears to establish that membrane transport coupled surface processes are predominant. This, along with the known dependence of certain cell regulatory processes upon ionic availability, has led to a unified kinetic approach to the electrochemical modulation of these phenomena. Thus, the kinetic coupling requirement of transport coupled surface processes establishes pulse duration ranges. Amplitude specificity provides guidelines for repetition rate ranges. Both, however, must be coupled with the requirements of overall kinetic coupling for which the entire cell regulatory process control loop needs to be taken into account. This has led to the perturbation/relaxation approach in which perturbation time can be varied by grouping pulses in a burst mode with concomitant repetition rate changes (relaxation time). Application of this overall approach to in vitro and in vivo cell systems, along with electrochemical kinetic data, provides strong circumstantial evidence that the postulated mechanistic pathways may indeed be key steps in cell regulation.