Muscimol

Potent, selective and competitive GABA_A receptor agonist and a potent partial GABA_A-ρ (GABAC) receptor agonist.

Muscimol is a GABA analog with comparable potency to GABA and is thought to act at the orthosteric site at GABA_A receptors in varying active conformations.

Also acts as a weak inhibitor of GABA uptake but is not a substrate for GABA transaminase.

Application of muscimol evokes GABA_AR currents and its actions are antagonized by the GABA_AR antagonist bicuculline (bicuculline methochloride, methiodide and methobromide also available).

Muscimol enhances inhibitory neurotransmission and suppresses spontaneous activity. It is commonly used in reversible brain inactivation studies.

Active in vivo and blood brain barrier permeable.

Shows psychoactive, memory impairing effects and anticonvulsant actions at high doses.

The GABA_A receptor agonist muscimol is used at concentrations of 1-50 µM. Muscimol from Hello Bio used at 10 µM led to a large hyperpolarising whole-cell current in hippocampal CA1 neurons (see Fig 1 above). Action of muscimol was fully blocked by the GABA_A receptor antagonist bicuculline (100 µM).

#Protocol 1: Assay used for muscimol

• Whole cell voltage clamp recordings of CA1 pyramidal neurons from the rat hippocampal brain slice.
• Neurons were held at 0 mV and GABA_A receptor currents were evoked via applying muscimol directly to the recording chamber during continuous perfusion.
• To test muscimol’s selectivity to GABA_A receptors the experiment was repeated within the same neuron in the presence of the GABA_A receptor antagonist bicuculline (100 µM).
• Under these conditions muscimol failed to induce a hyperpolarising current.