Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease

Endogenous direct-current electric fields (dcEFs) occur in vivo in the form of epithelial transcellular potentials or neuronal field potentials, and a variety of cells respond to dcEFs in vitro by directional movement. This is termed galvanotaxis. The passive influx of Ca(2+) on the anodal side should increase the local intracellular Ca(2+) concentration, whereas passive efflux and/or intracellular redistribution decrease the local intracellular Ca(2+) concentration on the cathodal side. These changes could give rise to 'push-pull' effects, causing net movement of cells towards the cathode. However, such effects would be complicated in cells that possess voltage-gated Ca(2+) channels and/or intracellular Ca(2+) stores. Moreover, voltage-gated Na(+) channels, protein kinases, growth factors, surface charge and electrophoresis of proteins have been found to be involved in galvanotaxis. Galvanotactic mechanisms might operate in both the short term (seconds to minutes) and the long term (minutes to hours), and recent work has shown that they might be involved in metastatic disease. The galvanotactic responses of strongly metastatic prostate and breast cancer cells are much more prominent, and the cells move in the opposite direction compared with corresponding weakly metastatic cells. This could have important implications for the metastatic process and has clinical implications. Galvanotaxis could thus play a significant role in both cellular physiology and pathophysiology.