Differential effects of sodium-free media on γ-aminobutyrate and muscimol-evoked conductance increases recorded from lobster muscle fibres

Membrane conductance increases evoked by γ-aminobutyric acid and muscimol were compared on single lobster muscle fibres. Muscimol was approximately 4 times more potent than γ-amino-butyric acid. The log-dose/conductance curves for γ-aminobutyrate and muscimol were parallel (with similar apparent maximum) and were fitted by a two independent binding-site receptor model (apparent dissociation constants were, respectively, 27 μM and 7 μM). Combination of γ-aminobutyrate with a fixed dose of muscimol did not reveal any mutual hindrance between agonists. Dose/conductance curves for 4,5,6,7-tetrahydroisoxazolo-pyridin-3-ol or isoguvacine also paralleled the curves for γ-aminobutyrate, but these agonists were about half as potent as γ-aminobutyrate. In 1 mM nipecotic acid, responses to γ-aminobutyrate (but not muscimol) were very slightly enhanced. In contrast, replacement of extracellular Na⁺ with Li⁺ or glucosamine consistently depressed responses to muscimol but had little or no effect on responses to γ-aminobutyrate. Use of choline as a Na⁺ substitute depressed the effects of both muscimol and γ-aminobutyrate, although a preferential depression of muscimol responses was still apparent. Two possible interpretations of our data are discussed: (1) that there may be two populations of inhibitory amino acid receptors on lobster muscle, one preferring muscimol (modulated by Na⁺), the other preferring γ-aminobutyrate (less affected by Na⁺ removal); (2) that Na⁺ can affect differentially the affinity of the same receptor site for a range of γ-aminobutyrate receptor agonists. Our results in Na⁺-free solutions therefore raise the possibility that γ-aminobutyrate and muscimol might not share an identical mechanism of action.