title: Directional movement of rat prostate cancer cells in direct-current electric field: involvement of voltagegated Na+ channel activity.
abstract: A two-part hypothesis has been tested, which proposes that (1) prostate cancer cells are galvanotactic (i.e. respond to an electric field by moving directionally) and (2) voltage-gated Na+ channel activity, which was shown previously to be expressed specifically by strongly metastatic cells, controls galvanotaxis. Two well-defined rat ('Dunning') cell lines, originally derived from the same prostate tumour but differing markedly in their metastatic ability, were used. Cells were exposed to exogenous direct-current electric fields of physiological strength (0.1-4.0 V cm(-1)), their reactions were recorded by light microscopy and analysed by a quantitative tracking method. Voltage-gated Na+ channel activity was modulated pharmacologically using a range of concentrations of a specific channel blocker (tetrodotoxin) or an opener (veratridine). The results showed that the highly metastatic MAT-LyLu cells responded to the application of the electric field strongly by migrating towards the cathode. By contrast, the weakly metastatic AT-2 cells gave no such response. Tetrodotoxin suppressed the galvanotactic response of the MAT-LyLu cells whereas veratridine enhanced it. Both compounds had little effect on the AT-2 cells. These results are consistent with functional voltage-gated Na+ channel expression occurring specifically in highly metastatic cells. This is also the first demonstration of control of galvanotaxis, in any cell type, by voltage-gated Na+ channel activity. The possible underlying mechanisms and the in vivo relevance of these findings are discussed.
authors.affiliation: Department of Biology, Imperial College of Science, Technology and Medicine, London, UK. m.djamgoz@ic.ac.uk
authors.lastname: Djamgoz MBA
authors.forename: M
authors.initials: M
authors.lastname: Mycielska
authors.forename: Z
authors.initials: Z
authors.lastname: Madeja
authors.forename: S P
authors.initials: SP
authors.lastname: Fraser
authors.forename: W
authors.initials: W
authors.lastname: Korohoda
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004574:Electromagnetic Fields; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D011471:Prostatic Neoplasms; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000502:physiology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D015222:Sodium Channels; D013779:Tetrodotoxin; D014701:Veratridine; D002118:Calcium