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- Title
Functional cardiac Na+ channels are expressed in human melanoma cells.
- Authors
Xie, An; Gallant, BENjamin; Guo, Hao; Gonzalez, Alfredo; Clark, Matthew; Madigan, Audrey; FENg, FENg; ChEN, Hong-Duo; Cui, Yali; Dudley, Samuel C.; Wan, YinshENg
- Abstract
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 (Nav1.5) 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.
- Subjects
MEMBRANE potential; METASTASIS; MELANOMA; HOMEOSTASIS; TETRODOTOXIN
- Publication
Oncology Letters, 2018, Vol 16, Issue 2, p1689
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2018.8865