Anesthetic effects on synaptic transmission and gain control in respiratory control.
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.
Stuth
Eckehard A
EA
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Stucke
Astrid G
AG
Brandes
Ivo F
IF
Zuperku
Edward J
EJ
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D006801:Humans; D009046:Motor Neurons / Q000187:drug effects; D012125:Respiratory Center / Q000166:cytology / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D000777:Anesthetics