Muscimol uptake, release and binding in rat brain slices.

Abstract

Abstract— The GABA analogue, muscimol, was taken up relatively inefficiently compared to GABA by slices of rat cerebral cortex at 37 C. Muscimol uptake followed saturation kinetics (Km ImM. Vm 0.1 μmol g mini and showed an absolute dependence on sodium ions. The relative susceptibilities of muscimol uptake and GABA high affinity uptake to a variety of inhibitors, including (‐)‐nipecotic acid. (+)‐2.4‐diaminobutyric acid and arecaidine, and the stimulation of muscimol efflux by 50μM‐GABA, suggest that muscimol and GABA share some common transport carriers. Since L‐histidine inhibited muscimol uptake hut not GABA high affinity uptake, at least part of the observed muscimol uptake may be mediated by the 'small basic’amino acid transport system. Muscimol appeared to he taken up into nerve terminals, since uptake was inhibited by the neuronal uptake inhibitor cis‐3‐aminocyclohexanecarboxylic acid but not by the glial uptake inhibitor β‐alanine. Muscimol efflux was stimulated in a calcium‐dependent manner by an increased potassium ion concentration.Sodium‐independent binding of muscimol was observed in slices of rat cerebral cortex at 4 C. Binding could be inhibited by a variety of substances. including GABA, isoguvacine and (+)‐bicuculline methochloride, which are known to inhibit the binding of muscimol to putative GABA receptors associated with synaptic membranes purified from rat brain.