The effects of brief anoxic episodes on intracellularly recorded CA3 pyramidal neurons have been studied in the hippocampal slice preparation.
Anoxia induced a depolarization occasionally preceded by a transient hyperpolarization associated with a fall in input resistance. The anoxic depolarization was due to the release of
glutamate from presynaptic terminals since it was blocked by
tetrodotoxin (TTX) (1 microM) or by the broad spectrum
excitatory amino acid antagonist kynurenate (1 mM). In the presence of TTX (1 microM) or
kynurenate (1 mM),
anoxia only induced a hyperpolarization which was due to activation of a K+ conductance. The anoxic depolarization was blocked by
galanin, a hormone which activates
ATP sensitive K+ (K+ATP) channels. Anoxic depolarization was increased by the potent sulfonylurea agent
glibenclamide (GLIB) which blocks K+ATP channels. Bath applications of these agents had little effect when applied in oxygenated
Krebs solution suggesting that their action may be mediated by K+ATP channels. Since excessive release of
glutamate during
anoxia is neurotoxic, agents such as
galanin which activate K+ATP channels may provide tissue specific protection against anoxic damage.