The effect of blocking sodium influx on anoxic damage in the rat hippocampal slice.
The in vitro rat hippocampal slice was used to study the effect of tetrodotoxin, a sodium channel blocker, on anoxic damage. Tetrodotoxin improved recovery of the evoked population spike after anoxia and reduced the fall in adenosine 5'-triphosphate during anoxia. Electrophysiological responses to perforant pathway stimulation were recorded in the dentate granule cell layer before, during and after 10 min of anoxia, with and without tetrodotoxin. Preincubation with tetrodotoxin permitted recovery of the evoked population spike to 43 +/- 10% (mean +/- standard error) in the post-anoxic period; this compared to 3 +/-3% recovery in untreated tissue (P less than 0.005). Similar studies of the CA1 pyramidal cells, which are more sensitive to anoxia, showed that tetrodotoxin improved recovery of the postsynaptic response after 5 min of anoxia. The recovery was 69 +/- 15% of its pre-anoxic level when treated with tetrodotoxin. This compares to no recovery in untreated tissue (P less than 0.005). Biochemical studies demonstrated a significantly reduced fall in adenosine 5'-triphosphate levels during levels in the dentate granule cell layer fell to 1.4 nM/mg dry wt, whereas following treatment with tetrodotoxin they only fell to 2.2 nM/mg. Since it required only 5 min of anoxia to damage the CA1 pyramidal cells, adenosine 5'-triphosphate levels were measured in this region after 5 min of anoxia. Adenosine 5'-triphosphate levels in the CA1 region fell to 2.2 nM/mg in untreated tissue after 5 min of anoxia, compared to 2.9 nM/mg in the tetrodotoxin-treated tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Boening
J A
JA
Department of Anesthesiology, State University of New York, Brooklyn 11203.
Kass
I S
IS
Cottrell
J E
JE
Chambers
G
G
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D012964:Sodium / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; D012964:Sodium