Selective GABA-receptor actions of amobarbital on thalamic neurons

We studied amobarbital's effects on membrane properties and currents, and electrically evoked inhibitory postsynaptic currents (IPSCs) mediated by γ-aminobutyric acid (GABA) in rat thalamic slices. Using concentration–response relationships, we compared amobarbital's effects in nociceptive nuclei and non-nociceptive nucleus reticularis thalami (nRT). Amobarbital decreased input resistance by activating GABAA receptors. Amobarbital produced a larger decrease in ventrobasal than nRT neurons. Amobarbital depressed burst and tonic firing. Depression of burst firing was more effective, particularly in ventrobasal and intralaminar neurons. Depression was reversed by GABAA antagonists, and surmountable by increasing current injection, implicating a receptor-mediated shunt mechanism. Amobarbital did not affect the tetrodotoxin-isolated low threshold Ca2+ spike during GABAA blockade. Amobarbital reduced excitability without altering outward leak, or hyperpolarisation-activated inward currents. Amobarbital increased mean conductance and burst duration of single GABAA channels. Consistent with this, amobarbital increased amplitude and decay time of IPSCs with distinct EC50s, implicating actions at two GABAA receptor sites. Activation of GABAA receptors by low concentrations, fast IPSC amplitude modulation, and failure to affect intrinsic currents distinguished amobarbital's mechanism of action from previously characterised barbiturates. The selective actions of amobarbital on GABAA receptor may have relevance in explaining anaesthetic and analgesic uses. British Journal of Pharmacology (2004) 143, 485–494. doi:10.1038/sj.bjp.0705974