Extracellular magnesium ion modifies the actions of volatile anesthetics in area CA1 of rat hippocampus in vitro

Background: Magnesium ion (Mg ²⁺) is involved in important processes as modulation of ion channels, receptors, neurotransmitter release, and cell excitability in the central nervous system. Although extracellular Mg ²⁺ concentration ([Mg ²⁺] _o) can be altered during general anesthesia, there has been no evidence for [Mg ²⁺] _o-dependent modification of anesthetic actions on neural excitability in central nervous system preparations. The purpose of current study was to determine whether the effects of volatile anesthetics are [Mg ²⁺] _o-dependent in mammalian central nervous system. Methods: Extracellular electrophysiologic recordings from CA1 neurons in rat hippocampal slices were used to investigate the effects of [Mg ²⁺] _o and anesthetics on population spike amplitude and excitatory postsynaptic potential slope. Results: The depression of population spike amplitudes and excitatory postsynaptic potential slopes by volatile anesthetics were significantly dependent on [Mg ²⁺] _o. The effects were attenuated in the presence of a constant [Mg ²⁺] _o/extracellular Ca ²⁺ concentration ratio. However, neither N-methyl-D -aspartate receptor antagonists nor a non-N-methyl-D-aspartate receptor antagonist altered the [Mg ²⁺] _o -dependent anesthetic-induced depression of population spikes. Volatile anesthetics produced minimal effects on input-output (excitatory postsynaptic potential-population spike) relations or the threshold for population spike generation. The effects were not modified by changes in [Mg ²⁺] _o. In addition, the population spike amplitudes, elicited via antidromic (nonsynaptic) stimulation, were not influenced by [Mg ²⁺] _o in the presence of volatile anesthetics. Conclusions: These results provide support that alteration of [Mg ²⁺] _o modifies the actions of volatile anesthetics on synaptic transmission and that the effects could be, at least in part, a result of presynaptic Ca ²⁺ channel-related mechanisms.