Functional cardiac Na channels are expressed in human melanoma cells.

Resting membrane potential (RMP) and intracellular Ca concentration [(Ca)] are involved in tumorigenesis and metastasis. The present study investigated whether functional cardiac Na channels are expressed in human melanoma cells (WM 266-4) and its nonmalignant human melanocytes (HMC), as well as whether they participate in RMP maintenance and Ca homeostasis. Confocal microscopy and western blot analysis were used to detect Na channels. The patch-clamp technique was employed to record Na currents and action potentials. Cytoplasmic Ca was measured by loading Fluo-4. Cardiac (Na1.5) Na channels were expressed in HMCs and WM 266-4 cells. Tetrodotoxin (TTX) dose-dependently blocked Na currents in WM 266-4 while HMCs had no Na currents. Ultraviolet light induced similar action potentials in HMCs and WM 266-4 cells, which were abolished by transient receptor potential A1 channel-specific blocker, HC-030031. Compared with HMCs, RMP was substantially depolarized in WM 266-4. TTX hyperpolarized RMP in WM 266-4 cells at a concentration of 30 µM, which facilitated Ca influx. Compared with HMCs, (Ca) was significantly higher in WM 266-4 cells and was elevated by 30 µM TTX. Collectively, Cardiac Na channels depolarize RMP and inhibit Ca uptake in melanoma cells possibly contributing to tumorigenesis and metastasis. Na channel agonists may be developed to treat melanoma such as WM 266-4.