Functional cardiac na+ channels are expressed in human melanoma cells

A. N. Xie, Benjamin Gallant, Han Guo, Alfredo Gonzalez, Matthew Clark, Audrey Madigan, Feng Feng, Hong Duo Chen, Yali Cui, Samuel C. Dudley, Yinsheng Wan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1689-1695
Number of pages7
JournalOncology Letters
Volume16
Issue number2
DOIs
StatePublished - Aug 2018

Bibliographical note

Funding Information:
This research project was supported by a grant from the National Institute of Health (grant no. P20RR016457; from the INBRE Program of the National Center for Research).

Keywords

  • Melanoma
  • Membrane potential
  • Na channel

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