Faculty Collaboration Database

Anesthetic effects on synaptic transmission and gain control in respiratory control. Respir Physiol Neurobiol 2008 Dec 10;164(1-2):151-9

Date

06/28/2008

Pubmed ID

18583201

DOI

10.1016/j.resp.2008.05.007

Scopus ID

2-s2.0-53849141477 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

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.

Author List

Stuth EA, Stucke AG, Brandes IF, Zuperku EJ

Authors

Astrid G. Stucke MD Professor in the Anesthesiology department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin
Edward J. Zuperku PhD, MS Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anesthetics
Animals
Dogs
Humans
Motor Neurons
Respiratory Center
Respiratory System
Synaptic Transmission