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Regulation and pharmacological blockade of sodium-potassium ATPase: a novel pathway to neuropathy

Additional Information

In addition to the implications for the development of neuropathies, the osmotic lysis due to simultaneous stimulation of upregulated sodium channels and pharmacological  blockade of Na+, K+-ATPase has potential therapeutic use.  Many metastatic epithelial cell carcinomas, such as breast, lung, prostate, cervical, ovarian, colon and pancreatic cancers, over-express voltage-gated sodium channels by a hundred-fold or more.  Therefore, the combination of sodium pump blockade and sodium channel stimulation may cause a selective lysis of tumor cells without damage to cells that do not over-express sodium channels (patent pending).  Such a treatment would be most effective in end-stage patients, and would obviate most of the morbidity associated with chemotherapy or radiation therapy.

Regulation and pharmacological blockade of sodium-potassium ATPase A novel pathway to neuropathy

 

 

 

 

 

 

 

 

 

 

 

 

Journal Reference

Paul D1, Soignier RD2, Minor L3, Tau H4, Songu-Mize E5, Gould HJ 3rd6. J Neurol Sci. 2014 May 15;340(1-2):139-43.

Show Affiliations

1 Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Anesthesiology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Physical Medicine and Rehabilitation, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States; Center of Excellence for Oral and Craniofacial Biology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Alcohol and Drug Abuse Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States. Electronic address: [email protected]

2 Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States.

3 Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, United States.
4 Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States.

5 Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States.

6 Department of Neurology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Anesthesiology, LSU Health Sciences Center, New Orleans, LA 70112, United States; Department of Physical Medicine and Rehabilitation, LSU Health Sciences Center, New Orleans, LA 70112, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA 70112, United States; Center of Excellence for Oral and Craniofacial Biology, LSU Health Sciences Center, New Orleans, LA 70112, United States.

 

 Abstract

Inflammation causes upregulation of NaV1.7 sodium channels in the associated dorsal root ganglia (DRG). The resultant increase in sodium influx must be countered to maintain osmotic homeostasis. The primary mechanism to pump sodium out of neurons is Na(+), K(+)-ATPase. To test whether there is a compensatory upregulation of Na(+), K(+)-ATPase after inflammation, rats received an injection of complete Freund’s adjuvant (CFA) into one hindpaw and saline into the contralateral hindpaw. Three days later, L4-L6 DRGs were extracted and analyzed using gel electrophoresis and immunohistochemistry. Immunoreactivity for both the {Alpha}-1 and {Alpha}-3 subunits were increased in DRG associated with CFA-treatment, compared to saline-treatment. To test whether dysregulation of Na(+), K(+)-ATPase may cause cell death after inflammation, we produced a pharmacological blockade with ouabain (10mg/kg, s.c.) three days after CFA injection and paws were stimulated or not. Twenty-four hours later, DRG were removed and stained with cresyl violet. Greater cell death was seen in DRG from ouabain-treated animals on the CFA treated side than the saline-treated side. Paw stimulation doubled this difference. Control DRG showed little neuronal death. These results are evidence that regulation of Na(+), K(+)-ATPase during major inflammatory disease states is critical for homeostatic protection of primary afferent neurons.

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