All volatile and most intravenous
general anesthetics currently in clinical use cause
respiratory depression at concentrations suitable for surgery. While various in vitro studies have identified potential molecular targets, their contributions to
respiratory depression are poorly understood. At surgical concentrations,
anesthetics principally affect
ligand-gated, rather than voltage-gated
ion channels. Here we focus on
anesthetic-induced effects on synaptic transmission in brainstem respiratory neurons. The spontaneous discharge patterns of canine respiratory bulbospinal premotor neurons in vivo depend principally on
NMDA and non-
NMDA receptor-mediated excitation, while GABAA receptors mediate gain modulation and silent-phase inhibition. Studies examining the effects of volatile
anesthetics on synaptic neurotransmission to these neurons suggest a primary role for postsynaptic enhancement of GABAA receptor function, partly offset by a reduction in presynaptic inhibition and a presynaptic reduction in glutamatergic excitation. In studies involving canine inspiratory hypoglossal motoneurons in vivo, which are already strongly depressed by low concentrations (< 0.5 MAC) of volatile
anesthetics, the role of
acid-sensitive, two-pore domain K+ (TASK) channels was found to be minimal at these subanesthetic concentrations. Potentiation of GABAA receptor-mediated inhibition was suggested. These studies on canine respiratory neurons provide valuable insights into mechanisms of
anesthetic depression within a respiratory control subsystem; future studies will be required to determine
anesthetic effects on sources of respiratory drive, rhythm, and their control.