The Journal of Neurophysiology Vol. 82 No. 5 November 1999, pp. 2812-2819
Copyright ©1999 by the American Physiological Society

RAPID COMMUNICATION

Sevoflurane Induced Suppression of Inhibitory Synaptic Transmission Between Soma-Soma Paired Lymnaea Neurons

 ¹Respiratory and Neuroscience Research Groups, Faculty of Medicine, The University of Calgary, Calgary, Alberta T2N 4N1, Canada; and  ²Department of Anesthesiology, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan

Hamakawa, Toshiro, Zhong-Ping Feng, Nikita Grigoriv, Takuya Inoue, Mayumi Takasaki, Sheldon Roth, Ken Lukowiak, Shabih U. Hasan, and Naweed I. Syed. Sevoflurane Induced Suppression of Inhibitory Synaptic Transmission Between Soma-Soma Paired Lymnaea Neurons. J. Neurophysiol. 82: 2812-2819, 1999. The cellular and synaptic mechanisms by which general anesthetics affect cell-cell communications in the nervous system remain poorly defined. In this study, we sought to determine how clinically relevant concentrations of sevoflurane affected inhibitory synaptic transmission between identified Lymnaea neurons in vitro. Inhibitory synapses were reconstructed in cell culture, between the somata of two functionally well-characterized neurons, right pedal dorsal 1 (RPeD1, the giant dopaminergic neuron) and visceral dorsal 4 (VD4). Clinically relevant concentrations of sevoflurane (1-4%) were tested for their effects on synaptic transmission and the intrinsic membrane properties of soma-soma paired cells. RPeD1- induced inhibitory postsynaptic potentials (IPSPs) in VD4 were completely and reversibly blocked by sevoflurane (4%). Sevoflurane also suppressed action potentials in both RPeD1 and VD4 cells. To determine whether the anesthetic-induced synaptic depression involved postsynaptic transmitter receptors, dopamine was pressure applied to VD4, either in the presence or absence of sevoflurane. Dopamine (10^]5 M) activated a voltage-insensitive K⁺ current in VD4. The same K⁺ current was also altered by sevoflurane; however, the effects of two compounds were nonadditive. Because transmitter release from RPeD1 requires Ca²⁺ influx through voltage-gated Ca²⁺ channels, we next tested whether the anesthetic-induced synaptic depression involved these channels. Individually isolated RPeD1 somata were whole cell voltage clamped, and Ca²⁺ currents were analyzed in control and various anesthetic conditions. Clinically relevant concentrations of sevoflurane did not significantly affect voltage-activated Ca²⁺ channels in RPeD1. Taken together, this study provides the first direct evidence that sevoflurane-induced synaptic depression involves both pre- and postsynaptic ion channels.