Excitatory and inhibitory synaptic mechanisms in anaesthesia.
To understand the cellular and molecular basis of the anaesthetic state, it is important to remember that, in the intact CNS, synapses operate within elaborate nerve networks. From the data presented above, it is evident that block of impulse conduction in presynaptic fibres does not explain the effects of most anesthetics on synaptic activity. This is not surprising since some anaesthetics, the barbiturates in particular, may both depress excitation and enhance inhibition. General anaesthetics modulate the activity of presynaptic voltage-gated calcium channels and this appears to be sufficient to account for the reduction in transmitter secretion they produce. Transmitter operated ion channels in the postsynaptic membrane are modulated by smaller concentrations of anaesthetics than are required to modulate the presynaptic voltage-gated calcium channels. For this reason, transmitter operated channels appear to represent a major target site for anaesthetics. Finally, there are subtle effects of anaesthetics on the patterns of impulse propagation in nerve axons and on action potential generation in the cell body which result from modulation of membrane excitability. The overall effect of an anaesthetic agent depends on summation of events occurring at the many individual synapses and neurones that make up the network. The effects of anaesthetics on different neuronal pathways may therefore depend on the nature of the receptors and ion channels of the cells that comprise the network. The anaesthetic state may be the result of all these actions, but the characteristics of the state may differ somewhat from agent to agent.
Pocock
G
G
Department of Physiology, Royal Free Hospital School of Medicine, London.
Richards
C D
CD
D000768:Anesthesia, General; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D000777:Anesthetics; D007473:Ion Channels; D018377:Neurotransmitter Agents