Functional cardiac na⁺ channels are expressed in human melanoma cells

Resting membrane potential (RMP) and intracellular Ca²⁺ concentration [(Ca²⁺)_i] 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 Ca²⁺ 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 Ca²⁺ was measured by loading Fluo-4. Cardiac (Na_v1.5) 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 Ca²⁺ influx. Compared with HMCs, (Ca²⁺)_i was significantly higher in WM 266-4 cells and was elevated by 30 µM TTX. Collectively, Cardiac Na⁺ channels depolarize RMP and inhibit Ca²⁺ uptake in melanoma cells possibly contributing to tumorigenesis and metastasis. Na⁺ channel agonists may be developed to treat melanoma such as WM 266-4.