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ANESTHETIC PHARMACOLOGY

Low Concentrations of Pentobarbital Enhance Excitability of Rat Hippocampal Neurons

David P. Archer, MD^*, and Sheldon H. Roth, PhD^*

From the Departments of *Anesthesia and Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to David P. Archer, MD, Department of Anesthesia, Foothills Medical Center, 1403 29th St, Calgary, Alberta, Canada T2N 2T9. Address e-mail to darcher{at}ucalgary.ca.

BACKGROUND: Although the excitation phase observed during anesthetic induction and emergence is familiar to anesthesiologists, the cellular mechanisms of this phenomenon are not well understood. At anesthetic concentrations approximately one-tenth those required for surgical anesthesia, subjects demonstrate increased responsiveness to noxious stimulation. We previously estimated that the decrease in nociceptive reflex threshold is maximal at pentobarbital concentrations of approximately 5 µM. Here we used the rat hippocampal slice preparation to examine whether 5 µM pentobarbital increases the excitability of neurons.

METHODS: Intracellular recordings were obtained from CA1 neurons during stimulation of the Schaffer collateral pathway. We examined the effect of pentobarbital on resting intrinsic membrane properties and stimulus-response relationships. Excitability was evaluated with the relationship between the synaptic signal strength, as indicated by the excitatory postsynaptic potential slope, and the probability of spiking (E-S relationship).

RESULTS: Pentobarbital increased the excitability of hippocampal neurons, as shown by an increased probability of spiking at any given synaptic signal strength (P = 0.002), an effect known as "E-S potentiation." Pentobarbital was associated with an increase in the input resistance of the neuron and a shift of the action potential threshold towards more negative values. Pentobarbital did not increase the excitatory postsynaptic potential slope at any given stimulus strength.

CONCLUSIONS: At a 5 µM concentration, pentobarbital increased E-S coupling by enhancing the excitability of the postsynaptic neurons. Pentobarbital induced changes in intrinsic membrane properties that may contribute to increased excitability.