Effect of Cell Cycle on Cell Surface Expression of Voltage-Gated Sodium Channels and Na+,K+-ATPase

Samantha Edenfield; Abigail M Sims; Constance Porretta; Harry J Gould 3rd; Dennis Paul

doi:10.3390/cells11203240

Effect of Cell Cycle on Cell Surface Expression of Voltage-Gated Sodium Channels and Na⁺,K⁺-ATPase

Cells. 2022 Oct 15;11(20):3240. doi: 10.3390/cells11203240.

Authors

Samantha Edenfield¹, Abigail M Sims¹, Constance Porretta², Harry J Gould 3rd^{3

4

5}, Dennis Paul^{1

3

4

5

6}

Affiliations

¹ Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
² Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
³ Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
⁴ Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
⁵ Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
⁶ Dental and Craniofacial Biology Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70119, USA.

Abstract

Voltage-gated sodium channels (VGSCs) are the target for many therapies. Variation in membrane potential occurs throughout the cell cycle, yet little attention has been devoted to the role of VGSCs and Na⁺,K⁺-ATPases. We hypothesized that in addition to doubling DNA and cell membrane in anticipation of cell division, there should be a doubling of VGSCs and Na⁺,K⁺-ATPase compared to non-dividing cells. We tested this hypothesis in eight immortalized cell lines by correlating immunocytofluorescent labeling of VGSCs or Na⁺,K⁺-ATPase with propidium iodide or DAPI fluorescence using flow cytometry and imaging. Cell surface expression of VGSCs during phases S through M was double that seen during phases G0-G1. By contrast, Na⁺,K⁺-ATPase expression increased only 1.5-fold. The increases were independent of baseline expression of channels or pumps. The variation in VGSC and Na⁺,K⁺-ATPase expression has implications for both our understanding of sodium's role in controlling the cell cycle and variability of treatments targeted at these components of the Na⁺ handling system.

Keywords: Na+,K+-ATPase; VGSCs; cell cycle; sodium pumps; voltage-gated sodium channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases* / metabolism
Cell Cycle
Cell Division
Cell Membrane / metabolism
Propidium
Sodium / metabolism
Voltage-Gated Sodium Channels* / metabolism

Substances

Adenosine Triphosphatases
Propidium
Voltage-Gated Sodium Channels
Sodium

Grants and funding

This research was funded by a grant from the Joe and Dorothy Brown Foundation and a research services contract with Oleander Medical Technologies, LLC (OMT).