(-)-Bicuculline methiodide

Methiodide salt form of (+)-bicuculline.

Prototypic, competitive GABA_A receptor antagonist which displaces GABA from the agonist binding site to prevent receptor activation. 

Also acts as a negative allosteric inhibitor of channel opening to inhibit GABA_A receptor activation by anaesthetic agents.

Additionally shows activity at SK calcium-activated potassium channels, nicotinic acetylcholine receptors and acetylcholinesterase.

Reversibly and competitively blocks GABA_A receptor mediated currents. Widely used to isolate glutamate receptor mediated EPSCs (excitatory postsynaptic potentials).

Shows convulsant action and induces epilepsy.

Freebase, methochloride and methobromide salts also available.

The GABA_A receptor antagonist bicuculline is commonly used to reduce levels of inhibition by blocking the actions of the neurotransmitter GABA. Bicuculline is commonly used at concentrations of 100 μM and above.

Bicuculline methiodide from Hello Bio reduces both spontaneous inhibitory post synaptic currents (IPSC) and evoked IPSCs (see Fig 1 above). It was effective at concentrations of 1 mM with complete receptor blockade at 100 μM.

#Protocol 1: Evoked and spontaneous inhibitory post synaptic currents (IPSCs)

• Whole cell voltage clamp recordings were obtained from layer V neurons of the mouse prelimbic cortex brain slice.
• A stimulating electrode was placed in layers II/III and IPSCs were evoked by a single square (150 μs) pulse every 10 sec at a stimulus intensity that gave a reliable IPSC.
• IPSCs were evoked at a range of neuron holding voltages to measure the reversal potential of the current to ensure it was GABAergic.
• Neurons were held at 0mV and IPSCs continuously stimulated and recorded in response to 5 min applications of varying concentrations of Bicuculline methiodide until complete receptor inhibition.
• Spontaneous IPSCs were recorded before and after addition of Bicuculline methiodide by holding the neuron at 0mV and recording for 10 sec.
• All recordings for IPSCs were made in the presence of AMPAR antagonists.