Selective GABA-receptor actions of amobarbital on thalamic neurons.
1. We studied amobarbital's effects on membrane properties and currents, and electrically evoked inhibitory postsynaptic currents (IPSCs) mediated by gamma-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). 2. Amobarbital decreased input resistance by activating GABA(A) receptors. Amobarbital produced a larger decrease in ventrobasal than nRT neurons. 3. Amobarbital depressed burst and tonic firing. Depression of burst firing was more effective, particularly in ventrobasal and intralaminar neurons. Depression was reversed by GABA(A) antagonists, and surmountable by increasing current injection, implicating a receptor-mediated shunt mechanism. 4. Amobarbital did not affect the tetrodotoxin-isolated low threshold Ca(2+) spike during GABA(A) blockade. Amobarbital reduced excitability without altering outward leak, or hyperpolarisation-activated inward currents. 5. Amobarbital increased mean conductance and burst duration of single GABA(A) channels. Consistent with this, amobarbital increased amplitude and decay time of IPSCs with distinct EC(50)s, implicating actions at two GABA(A) receptor sites. 6. Activation of GABA(A) 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 GABA(A) receptor may have relevance in explaining anaesthetic and analgesic uses.
Kim
H-S
HS
Department of Anesthesia, The University of British Columbia, Vancouver, BC, Canada V5Z 4E3.
Wan
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X
Mathers
D A
DA
Puil
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E
D000654:Amobarbital / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000187:drug effects* / Q000502:physiology
D011963:Receptors, GABA-A; D000654:Amobarbital