Sevoflurane induced suppression of inhibitory synaptic transmission between soma-soma paired Lymnaea neurons

The cellular and synaptic mechanisms by which general anesthetics affect ce ll-cell communications in the nervous system remain poorly defined. In this study, we sought to determine how clinically relevant concentrations of se voflurane affected inhibitory synaptic transmission between identified Lymn aea neurons in vitro. Inhibitory synapses were reconstructed in cell cultur e, between the somata of two functionally well-characterized neurons, right pedal dorsal I (RPeD1, the giant dopaminergic neuron) and visceral dorsal 4 (VD4). Clinically relevant concentrations of sevoflurane (1-4%) were test ed for their effects on synaptic transmission and the intrinsic membrane pr operties of somasoma paired cells. RPeD1- induced inhibitory postsynaptic p otentials (IPSPs) in VD4 were completely and reversibly blocked by sevoflur ane (4%). Sevoflurane also suppressed action potentials in both RPeD1 and V D4 cells. To determine whether the anesthetic-induced synaptic depression i nvolved postsynaptic transmitter receptors, dopamine was pressure applied t o VD4, either in the presence or absence of sevoflurane. Dopamine (10(-15) M) activated a voltage-insensitive K+ current in VD4. The same K+ current w as also altered by sevoflurane; however, the effects of two compounds were nonadditive. Because transmitter release from RPeD1 requires Ca2+ influx th rough voltage-gated Ca2+ channels, we next tested whether the anesthetic-in duced synaptic depression involved these channels. Individually isolated RP eD1 somata were whole cell voltage clamped, and Ca2+ currents were analyzed in control and various anesthetic conditions. Clinically relevant concentr ations of sevoflurane did not significantly affect voltage-activated Ca2+ c hannels in RPeD1. Taken together, this study provides the first direct evid ence that sevoflurane-induced synaptic depression involves both pre- and po stsynaptic ion channels.