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Loss of functional voltage-gated sodium channels in persistent mumps virus-infected PC12 cells
1Department of Physiology, School of Medicine, University of Minnesota-Duluth 55812-2487.
Abstract:
Rat pheochromocytoma (PC12) cells, persistently infected with mumps virus (MV), failed to generate full-sized stimulus-evoked action potentials (SEAPs) when examined by intracellular electrophysiological recording techniques. Application of tetrodotoxin (TTX) had little or no effect on MV-reduced SEAPs, indicating that the number of functional voltage-gated Na+ channels was decreased or their operation was blocked by the virus. In contrast, MV-infected cells generated normal Ca2+ spikes when bathed in a solution containing TTX, tetraethylammonium ions and a high concentration (20 mM) of Ca2+. In addition, when infected cells bathed in TTX were superfused with Co2+ the SEAP profile reverted to that typical of PC12 cells with functional voltagegated K+ channels only. These observations indicate that MV affects voltage-gated Na+ channels, but spares voltage-gated Ca2+ and K+ channels of persistently infected cells.
Insights
Mumps virus (MV) infection in rat PC12 cells impairs sodium channels, preventing normal action potentials. However, calcium and potassium channels remain functional, suggesting MV specifically targets voltage-gated sodium channels.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- Mumps virus (MV) can establish persistent infections in host cells.
- Neuronal function relies on voltage-gated ion channels, including sodium (Na+), calcium (Ca2+), and potassium (K+) channels.
Purpose of the Study:
- To investigate the impact of persistent mumps virus infection on ion channel function in rat pheochromocytoma (PC12) cells.
- To determine which specific voltage-gated ion channels are affected by MV infection.
Main Methods:
- Intracellular electrophysiological recordings were used to examine stimulus-evoked action potentials (SEAPs) in MV-infected PC12 cells.
- Pharmacological agents including tetrodotoxin (TTX), tetraethylammonium ions, and cobalt ions (Co2+) were applied to assess ion channel function.
Main Results:
- MV-infected PC12 cells exhibited reduced SEAPs, with TTX showing minimal effect, suggesting impaired voltage-gated Na+ channel function.
- MV-infected cells generated normal Ca2+ spikes in the presence of TTX and high extracellular Ca2+.
- Superfusion with Co2+ in TTX-treated cells restored a SEAP profile characteristic of functional voltage-gated K+ channels only.
Conclusions:
- Persistent mumps virus infection in PC12 cells significantly affects voltage-gated Na+ channels.
- Voltage-gated Ca2+ and K+ channels appear to be spared from the detrimental effects of MV infection in these cells.