Serum concentration modifies amplitude and kinetics of voltage-gated Na + current in the Mat-LyLu cell line of rat prostate cancer

Abstract

Voltage-gated Na + channel (VGSC) expression has previously been shown to be upregulated in strongly metastatic prostate cancer cells (rat and human) and its activity shown to potentiate a variety of cellular behaviours integral to the metastatic cascade. However, the mechanism(s) responsible for the Na + channel upregulation is not known. As a step towards evaluating the role of the extracellular biochemical environment in this regard, we have determined the effects of serum concentration on characteristics of Na + channel expressed in the strongly metastatic Mat-LyLu rat prostate cancer cell line. Whole-cell patch-clamp recording techniques were used to study the effects of serum concentrations, above and below the normal 1%. Both the amplitude and the kinetics of the currents were analysed. The following results were obtained: (1) Adding 1% foetal calf serum to cells starved of serum for 24 h increased Na + current density; however, increasing serum concentration further (to 5%) caused a reduction. (2) Serum-free medium produced Na + currents with slower kinetics of activation (time to peak) and inactivation (exponential decay). (3) Increased serum concentration (a) shifted steady-state inactivation to more positive potentials without affecting conductance and (b) increased tetrodotoxin sensitivity. It is concluded that serum concentration is an important determinant of the Na + channel characteristics leading to possible transcriptional and post-translational modifications of channel expression and/or activity. Experiments are now needed to determine which constituents (protein hormones, growth factors, etc.) are responsible for these effects.