title: Mechanical injury alters volume activated ion channels in cortical astrocytes.
abstract: Although astrocytic swelling is likely to mediate brain edema and high ICP after traumatic brain injury, the mechanism is not understood. We employed whole cell patch clamp electrophysiology and a stretch injury model to understand whether volume regulating ion currents are altered following cell injury. Mixed rat astrocytes and neurons were co-cultured on deformable silastic membranes. Mild-moderate cell injury was produced using a timed pulse of pressurized air to deform the silastic substrates by 6.5 mm. Then, ion currents were recorded with patch clamp methods. Cells were held at -65 mV and were stepped to +10 mV to monitor current changes.
  
  
  RESULTS
  In unstretched astrocytes, small amplitude currents were obtained under isotonic conditions. Hypotonic solution activated an outwardly-rectifying current which reversed near -40 mV. This current resembled a previously reported anion current whose activation may restore cell volume by mediating a net solute efflux. In contrast, stretch injured cells exhibited a large amplitude, nonrectifying current. This current was not due to non-specific ionic leakage, since it was fully suppressed by the cation channel blocker gadolinium. Activation of novel stretch-activated cation currents may exacerbate cell swelling in injured astrocytes. Stretch injured astrocytes thus express a dysfunctional cation current as opposed to an osmoregulatory anion current. This mechanism, if present in vivo, may contribute to the cytotoxic swelling seen after traumatic brain injury.
authors.affiliation: Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Virginia, USA.
authors.forename: X
authors.initials: X
authors.lastname: Di
authors.forename: P B
authors.initials: PB
authors.lastname: Goforth
authors.forename: R
authors.initials: R
authors.lastname: Bullock
authors.forename: E
authors.initials: E
authors.lastname: Ellis
authors.forename: L
authors.initials: L
authors.lastname: Satin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001929:Brain Edema / Q000503:physiopathology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000293:injuries* / Q000503:physiopathology; D007424:Intracellular Fluid / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology*; D051381:Rats; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D007473:Ion Channels