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Protein phosphotyrosine phosphatase inhibitors suppress regulatory volume decrease and the volume-sensitive Cl-
S M Thoroed1, A Bryan-Sisneros, P Doroshenko
1Loeb Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada.
Pflugers Archiv : European Journal of Physiology
|June 17, 1999
Summary
Protein tyrosine phosphatase (PTP) inhibitors, pervanadate and dephostatin, suppress regulatory volume decrease (RVD) and volume-sensitive chloride currents in mouse L-fibroblasts. This indicates PTP inhibition impacts cell volume regulation and ion transport.
Area of Science:
- Cellular Physiology
- Molecular Biology
- Biochemistry
Background:
- Regulatory volume decrease (RVD) is crucial for cell volume homeostasis.
- Volume-sensitive chloride currents play a key role in RVD.
- Protein tyrosine phosphatases (PTPs) are implicated in cellular signaling pathways.
Purpose of the Study:
- To investigate the effects of PTP inhibitors on RVD in mouse L-fibroblasts.
- To determine the impact of PTP inhibition on volume-sensitive chloride currents.
- To elucidate the role of PTPs in cell volume regulation.
Main Methods:
- Video microscopy for observing cell volume changes.
- Whole-cell patch-clamp technique for measuring chloride currents.
- Treatment with PTP inhibitors: pervanadate, monoperoxo(picolinato)-oxo-vanadate(V) [mpV(pic)], and dephostatin.
Main Results:
- Pervanadate, mpV(pic), and dephostatin significantly suppressed RVD induced by hyposmotic shock.
- PTP inhibitors reduced the acceleration of RVD caused by gramicidin.
- Pervanadate and dephostatin inhibited both outward and inward volume-sensitive chloride currents.
Conclusions:
- PTP inhibition suppresses RVD in mouse L-fibroblasts.
- PTP inhibitors affect the volume-sensitive chloride conductance.
- Inhibition of PTPs leads to the suppression of both RVD and volume-sensitive chloride currents, similar to findings in bovine chromaffin cells.