Effects of intravenous general anesthetics on [3H]GABA release from rat cortical synaptosomes.

TitleEffects of intravenous general anesthetics on [3H]GABA release from rat cortical synaptosomes.
Publication TypeJournal Article
Year of Publication1998
AuthorsMurugaiah KD, Hemmings HC
JournalAnesthesiology
Volume89
Issue4
Pagination919-28
Date Published1998 Oct
ISSN0003-3022
KeywordsAminobutyrates, Anesthesia, General, Anesthetics, Intravenous, Animals, Baclofen, Bicuculline, Calcium, Cerebral Cortex, GABA Agonists, GABA Antagonists, GABA-A Receptor Agonists, GABA-A Receptor Antagonists, gamma-Aminobutyric Acid, Male, Nerve Endings, Nipecotic Acids, Picrotoxin, Potassium Chloride, Proline, Propofol, Rats, Rats, Sprague-Dawley, Reproducibility of Results, Synaptic Transmission, Synaptosomes, Tritium
Abstract

BACKGROUND: Potentiation by general anesthetics of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission in the central nervous system is attributed to GABA(A) receptor-mediated postsynaptic effects. However, the role of presynaptic mechanisms in general anesthetic action is not well characterized, and evidence for anesthetic effects on GABA release is controversial. The effects of several intravenous general anesthetics on [3H]GABA release from rat cerebrocortical synaptosomes (isolated nerve terminals) were investigated.

METHODS: Purified synaptosomes were preloaded with [3H]GABA and superfused with buffer containing aminooxyacetic acid and nipecotic acid to inhibit GABA metabolism and reuptake, respectively. Spontaneous and elevated potassium chloride depolarization-evoked [3H]GABA release were evaluated in the superfusate in the absence or presence of various anesthetics, extracellular Ca2+, GABA receptor agonists and antagonists, and 2,4-diaminobutyric acid.

RESULTS: Propofol, etomidate, pentobarbital, and alphaxalone, but not ketamine, potentiated potassium chloride-evoked [3H]GABA release (by 1.3 to 2.9 times) in a concentration-dependent manner, with median effective concentration values of 5.4 +/- 2.8 microM (mean +/- SEM), 10.1 +/- 2.1 microM, 18.8 +/- 5.8 microM, and 4.4 +/- 2.0 microM. Propofol also increased spontaneous [3H]GABA release by 1.7 times (median effective concentration = 7.1 +/- 3.4 microM). Propofol facilitation of [3H]GABA release was Ca2+ dependent and inhibited by bicuculline and picrotoxin, but was insensitive to pretreatment with 2,4-diaminobutyric acid, which depletes cytoplasmic GABA pools.

CONCLUSIONS: Low concentrations of propofol, etomidate, pentobarbital, and alphaxalone facilitated [3H]GABA release from cortical nerve terminals. General anesthetics may facilitate inhibitory GABA-ergic synaptic transmission by a presynaptic mechanism in addition to their well-known postsynaptic actions.

Alternate JournalAnesthesiology
PubMed ID9778010
Grant ListGM 52441 / GM / NIGMS NIH HHS / United States