Low Concentrations of Pentobarbital Enhance Excitability of Rat Hippocampal Neurons

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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.

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