Related Experiment Video
Updated: Feb 5, 2026

Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors
Published on: February 10, 2014
Molecular Neuroprotection Induced by Zinc-Dependent Expression of Hepatitis C-Derived Protein NS5A Targeting Kv2.1
Jason A Justice1, Daniel T Manjooran1, Chung-Yang Yeh1
1Departments of Neurobiology (J.A.J., C.-Y.Y., K.A.H.-S., A.J.S., G.J.K., S.M., E.A.) and Pharmacology and Chemical Biology (D.T.M., M.J.P.) and Pittsburgh Institute for Neurodegenerative Diseases (J.A.J., D.T.M., C.-Y.Y., K.A.H.-S., A.J.S., G.J.K., S.M., M.J.P., E.A.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Abstract:
We present the design of an innovative molecular neuroprotective strategy and provide proof-of-concept for its implementation, relying on the injury-mediated activation of an ectopic gene construct. As oxidative injury leads to the intracellular liberation of zinc, we hypothesize that tapping onto the zinc-activated metal regulatory element (MRE) transcription factor 1 system to drive expression of the Kv2.1-targeted hepatitis C protein NS5A (hepatitis C nonstructural protein 5A) will provide neuroprotection by preventing cell death-enabling cellular potassium loss in rat cortical neurons in vitro. Indeed, using biochemical and morphologic assays, we demonstrate rapid expression of MRE-driven products in neurons. Further, we report that MRE-driven NS5A expression, induced by a slowly evolving excitotoxic stimulus, functionally blocks injurious, enhanced Kv2.1 potassium whole-cell currents and improves neuronal viability. We suggest this form of "on-demand" neuroprotection could provide the basis for a tenable therapeutic strategy to prevent neuronal cell death in neurodegeneration.
More Related Videos
Related Concept Videos
Antiepileptic Drugs: Potassium Channel Activators
Ezogabine has gained approval as an adjunctive treatment...
Molecular Chaperones and Protein Folding
The...
Molecular Chaperones and Protein Folding
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
G-Protein Gated Ion Channels
Sensory...
Hepatic Drug Clearance: Effect of Protein Binding
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...

