TY - JOUR
T1 - Mechanical injury alters volume activated ion channels in cortical astrocytes.
AU - Di, X.
AU - Goforth, P. B.
AU - Bullock, R.
AU - Ellis, E.
AU - Satin, L.
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1007/978-3-7091-6346-7_79
DO - 10.1007/978-3-7091-6346-7_79
M3 - Article
C2 - 11450049
AN - SCOPUS:0034570710
VL - 76
SP - 379
EP - 383
JO - Acta Neurochirurgica, Supplement
JF - Acta Neurochirurgica, Supplement
SN - 0065-1419
ER -