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Volume-sensitive purinergic signaling in human hepatocytes
A P Feranchak1, J G Fitz, R M Roman
1Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA. drew.feranchak@UCHSC.edu
Journal of Hepatology
|August 22, 2000
Summary
Human hepatocytes release adenosine 5'-triphosphate (ATP) both normally and when swelling. This extracellular ATP is crucial for regulating chloride permeability and cell volume in the liver.
Area of Science:
- Hepatology
- Cell Physiology
- Purinergic Signaling
Background:
- Purinergic signaling plays a role in liver function.
- Adenosine 5 -triphosphate (ATP) is involved in purinergic signaling.
Purpose of the Study:
- Characterize ATP release from human hepatocytes.
- Determine the role of extracellular ATP in autocrine regulation of chloride (Cl-) permeability and cell volume homeostasis.
Main Methods:
- Measured ATP release using a luciferase-luciferin assay.
- Assessed Cl- currents via whole-cell patch clamp.
- Quantified cell volume using a Coulter Multisizer.
Main Results:
- Hepatocyte swelling significantly increased extracellular ATP levels.
- Hypotonic conditions and ATP activated outward rectifying Cl- currents.
- Extracellular ATP removal and anion channel blockers inhibited volume-sensitive currents and impaired cell volume recovery.
Conclusions:
- Human hepatocytes exhibit constitutive and volume-dependent ATP release.
- Extracellular ATP is critical for regulating membrane Cl- permeability and cell volume.
- ATP release serves as an extracellular signal linking cellular hydration to hepatic functions.