Functional voltage-gated Na⁺ channels (VGSCs) have previously been shown to be expressed in strongly metastatic rat (MAT-LyLu) and human (PC-3) prostate cancer cells where VGSC activity enhanced in vitro invasion (Grimes et al. 1995; Laniado et al. 1997). In the present study, we have investigated whether long-term suppression of the VGSC could ultimately influence its subsequent functional activity.

The whole-cell voltage clamp technique was used to investigate the cells’ response to pre-incubation with 1 µM tetrodotoxin (TTX) for 1-3 days starting 3 h after seeding. Current-voltage relationships were analysed.

Pre-treatment with TTX for 2 or 3 days (but not 1 day) significantly reduced peak inward current density (Table 1). This effect was almost entirely reversible. On the other hand, values for activation voltage and voltage corresponding to peak current did not change. Preincubation with 20 nM TTX for 3 days did not cause any effect.

The results indicate that pre-incubation with TTX can reduce functional VGSC activity in MAT-LyLu cells, and that this effect is both dose- and time-dependent. The time dependence of this phenomenon suggests a positive feedback mechanism possibly involving transcriptional regulation. As VGSCs have been shown to be involved in potentiating several components of the metastatic cascade, the data presented here raise the possibility that inhibition of the VGSC by a long-term drug treatment regime might be a useful, novel approach to combating prostate cancer progression.

This work was supported by a MRC Priority Area (Prostate Cancer) PhD studentship.