Enflurane-induced burst discharge of hippocampal CA1 neurones is blocked by the NMDA receptor antagonist APV.
The basis for the hyperexcitability and seizure activity associated with enflurane anaesthesia was investigated using extracellular and intracellular recording in rat hippocampal brain slices. Enflurane produced seizure-like burst discharges in CA1 pyramidal neurones, accompanied by depressed field potential amplitudes and a reduced threshold for synaptically evoked population spikes. However, threshold for action potentials evoked by intracellular current injection did not change, nor did action potential amplitude, duration or spike frequency accommodation in single neurones. Enflurane 2.0 vol% hyperpolarized CA1 neurones (3.1 (SD 1.3)mV), decreased membrane conductance (12 (6)% below control), and depressed EPSP amplitudes (34% of control) (P less than 0.01). Enflurane appeared to enhance both intrinsic and synaptically mediated inhibitory potentials. The N-methyl-D-aspartate (NMDA) receptor antagonist amino-phosphonovalerate (APV) 5-20 mumol litre-1 completely blocked seizure-like burst discharge of CA1 neurones in the presence of enflurane, and the enflurane-induced reduction of population spike threshold; it did not alter anaesthetic depression of EPSP amplitude. Thus enflurane-induced burst discharge of CA1 neurones appeared to involve an enhancement of excitatory synaptic transmission rather than depression of intrinsic or synaptic inhibition.
MacIver
M B
MB
Department of Anesthesia, Stanford University School of Medicine, Ca. 94305-5117.
Kendig
J J
JJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D004737:Enflurane / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology; D013569:Synapses / Q000502:physiology
D000777:Anesthetics; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; D004737:Enflurane