SR 95531 hydrobromide (Gabazine)

SR 95531 hydrobromide (Gabazine) is a selective and competitive GABA_A receptor antagonist (K_i = 150 nM for displacement of [³H]-GABA from rat membranes).

SR 95531 (Gabazine) displaces GABA from the GABA_AR agonist binding site to prevent receptor activation. It also acts as a negative allosteric inhibitor of channel opening to inhibit GABA_A receptor activation by anaesthetic agents. It also displays low affinity glycine receptor inhibition.

SR 95531 (Gabazine) inhibits GABA-induced Cl- currents to reduce GABA-mediated synaptic inhibition.

SR 95531 additionally shows convulsive actions.

Gabazine (SR 95531) is commonly used to reduce levels of inhibition by antagonising GABA_A receptors. It is commonly used at concentrations between 10 – 200 μM.

Gabazine (SR 95531) from Hello Bio blocks spontaneous inhibitory post synaptic currents (IPSC) and evoked IPSCs (see Fig 1 above). It was effective at 1 μM and completely blocked GABA_A receptors at 20 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 Gabazine until complete receptor inhibition.
• Spontaneous IPSCs were recorded before and after addition of Gabazine by holding the neuron at 0mV and recording for 10 sec.
• All recordings for IPSCs were made in the presence of AMPAR antagonists.