title: 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 24h 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.
authors.affiliation: Neuroscience Solutions to Cancer Research Group, Department of Biological Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Ding
authors.forename: Mustafa B A
authors.initials: MB
authors.lastname: Djamgoz
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D004553:Electric Conductivity; D005312:Fetal Blood / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015222:Sodium Channels; D013779:Tetrodotoxin