Mechanisms by which extracellular magnesium ion modulates general anesthetic actions in CA1 of the rat hippocampus

It has been known that magnesium ion serves as a cofactor for many enzymes and affects binding activities of various receptor proteins. In the central nervous systems, magnesium competes with calcium at the calcium channels, attenuates the neurotransmitter releases from pre-synaptic terminals, and regulates the activation of the N-methyl-D-aspartate (NMDA) receptor. Our previous clinical studies demonstrated that intravenous administration of acetated Ringer solution decreased the extracellular magnesium ion concentrating [Mg] during general anesthesia. In the present study, we have studied the relationships between [Mg] and the actions of general anesthetics, and mechanisms for the [Mg]-dependent modulation of anesthetic actions. Extracellular recordings were used to record field potentials in rat CA1 pyramidal neurons of transverse hippocampal slices, stimulated electrically via Schaffer collateral fibers input. The depression of the population spike (PS) and excitatory post synaptic potential (EPSP) amplitude by volatile anesthetics (sevoflurane, isoflurane) was strongly dependent on [Mg]. Since the intravenous anesthetic (thiopental) failed to induce the [Mg]-dependent depression of PS, further experiments were then conducted to assess mechanism(s) for the volatile anesthetic-induced [Mg]-dependent modulation. The [Mg]-dependency was not affected by application of NMDA and/or non-NMDA receptor antagonists. The [Mg]-dependency, however, was attenuated under conditions where extracellular [Mg]/[Ca] ratio was constant. The antidromic PS, which was elicited via non-synaptic pathway, was not influenced by [Mg] in the presence and absence of volatile anesthetics. Authors concluded (1) that alteration of [Mg] can modulate the actions of volatile anesthetics on the Schaffer collateral fiber input to CA1 pathway, and (2) that the modulation could be a result of pre-synaptic calcium channel-related mechanisms.