Propofol and isoflurane enhancement of tonic gamma-aminobutyric acid type a current in cardiac vagal neurons in the nucleus ambiguus.
BACKGROUND
General anesthesia with propofol and isoflurane induces alterations of the cardiovascular system, including hypotension and changes in heart rate. The preganglionic cardiac vagal neurons (CVNs) are one of the major central components controlling heart rate and autonomic regulation. In this study, we examined whether propofol and isoflurane act on phasic or tonic gamma-aminobutyric acid type A (GABA(A)) receptor-mediated inhibition in CVNs.


METHODS
CVNs were identified in vitro by retrograde fluorescent labeling. Phasic and tonic GABA currents in CVNs were examined using the whole cell patch-clamp technique.


RESULTS
Propofol (10 microM) increased the membrane holding currents by 63 +/- 13% and prolonged the decay time of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) from 42.3 +/- 2.8 ms in control to 61.8 +/- 4.5 ms. Isoflurane, at concentrations of 100, 300, and 500 microM, decreased GABAergic mIPSCs frequency by 26.0 +/- 16%, 64.6 +/- 10.4%, and 70.5 +/- 9.8%, prolonged the decay time of GABAergic mIPSCs from 47.9 +/- 7.3 to 64.5 +/- 8.1 ms, 70.3 +/- 10.4 ms, and 66.8 +/- 8.1 ms, and increased the membrane holding currents by 32.8 +/- 12.8%, 42.7 +/- 10%, and 39.9 +/- 3%, respectively. The GABAergic antagonist gabazine (25 microM) blocked GABAergic mIPSCs, but failed to alter the enhanced holding potential induced by propofol and isoflurane. In contrast, the channel blocker of GABA(A) receptors, picrotoxin (100 microM), reversed the propofol and isoflurane-evoked increase in membrane holding current.


CONCLUSIONS
The results demonstrate that the general anesthetics propofol and isoflurane enhance both phasic and tonic GABA(A) receptor-mediated inhibition of CVNs.
Wang
Xin
X
Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA. xinwang@gwu.ed
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D053444:Inhibitory Postsynaptic Potentials; D007530:Isoflurane / Q000494:pharmacology*; D055369:Miniature Postsynaptic Potentials; D009433:Neural Inhibition / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D007530:Isoflurane; D015742:Propofol