Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured XXXX hippocampal neurons.

@entity1246 @entity1508 @entity73 @entity460 @entity35 @entity5161 @entity4488
1. The effects of the volatile anesthetics @entity4488 , @entity1508 , and @entity5161 on @entity1246 ( @entity1246 ) receptor-mediated inhibitory postsynaptic currents (IPSCs) were studied in cultured @entity35 hippocampal neurons. The experimental concentrations of anesthetics were measured directly using gas chromatography. All three anesthetics increased the overall duration of IPSCs, measured as the time to half-decay (T1/2). Clinically effective concentrations of anesthetics [between 0.5 and 1.5 times MAC (minimum alveolar concentration)] produced between 100 and 400% increases in T1/2. These effects were fully reversible, and did not involve alterations in the reversal potential for the IPSC (EIPSC). 2. The decay of the IPSC was fitted as a sum of two exponential functions, yielding a fast component (tau fast = 20 ms), and a slow component (tau slow = 77 ms), such that the fast component accounted for 79% of the IPSC amplitude and 52% of the total charge transfer. All three anesthetics produced concentration-related @entity73 , while simultaneously decreasing the amplitude and charge transfer of the fast component. Thus T1/2 approximated tau fast under control conditions, but approximated tau slow in the presence of the anesthetics. 3. Varying the @entity460 chelating agents in the recording pipettes had no effect on the quality or magnitude of alterations in IPSC kinetics produced by @entity1508 , suggesting that variations in intracellular @entity460 levels are not required for the effect of @entity1508 on the time course of the IPSC. 4. The (+)-stereoisomer of @entity5161 produced greater increases in the duration of the IPSC than the (-)-isomer when applied at approximately equal concentrations, suggesting that there is a structurally selective site of interaction for @entity5161 that modulates the GABAA receptor. 5. These results suggest that the previously shown abilities of volatile anesthetics to potentiate responses to exogenously applied @entity1246 and to prolong the duration of @entity1246 -mediated synaptic inhibition may be due to an alteration in the gating kinetics of the GABAA receptor/channel complex. Prolongation of synaptic inhibition in the CNS is consistent with the physiological effects that accompany anesthesia and may contribute to the mechanism of anesthetic action.
