Many inhaled anesthetics enhance the effect of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), supporting the view that the GABAA receptor could mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation (i.e., MAC, the minimum alveolar concentration required to suppress movement in response to a noxious stimulus in 50% of subjects). How...

UNLABELLED The ventrolateral periaqueductal gray (vlPAG) is a key structure in the descending pain modulatory circuit. Activation of the circuit occurs via disinhibition of GABAergic inputs onto vlPAG output neurons. In these studies, we tested the hypothesis that GABAergic inhibition is increased during persistent inflammation, dampening activation of the descending circuit from the vlPAG. Our...

Benzodiazepine (BZ) binding site ligands are important central nervous system (CNS) drugs. Their numbers and our knowledge of how they interact with the BZ-binding site of GABAA receptors are both rapidly expanding. The GABAA receptor is a member of the ligand-gated ion channel superfamily. In general, it consists of an assembly of transmembrane pentamers of different subunit compositions (1). ...

The efficacy of fast synaptic inhibition is critically dependent on the accumulation of GABAA receptors at inhibitory synapses, a process that remains poorly understood. Here, we examined the dynamics of cell surface GABAA receptors using receptor subunits modified with N-terminal extracellular ecliptic pHluorin reporters. In hippocampal neurons, GABAA receptors incorporating pHluorin-tagged su...

Objective: Isoflurane is widely used for inhaled general anesthesia. However, the mechanisms of isoflurane-induced cardiovascular depression are not fully understood. The effect of isoflurane on GABAA receptor expression in the NTS may underlie cardiovascular depression. Methods: The blood pressure (BP) and heart rates (HR) of conscious rats were confirmed initially using a CODA non-invasive bl...

αβγ GABAA receptor currents are phasic and desensitizing while αβδ GABAA receptor currents are tonic and have no fast desensitization. αβγ receptors are subsynaptic and mediate phasic inhibition while αβδ receptors are extra or peri-synaptic and mediate tonic inhibition. Given the different roles of these GABAA receptor isoforms and that GABAA receptors are allosterically regulated by extracell...

Attenuated behavioral sensitivity to neurosteroids has been reported for mice deficient in the GABAA receptor subunit. We therefore investigated potential subunit-specific neurosteroid pharmacology of the following GABAA receptor isoforms in a transient expression system: 1 3 2L, 1 3 , 6 3 2L, and 6 3 . Potentiation of submaximal GABAA receptor currents by the neurosteroid tetrahydrodeoxycortic...

Auditory steady-state auditory responses (ASSRs), in which the evoked potential entrains to stimulus frequency and phase, are reduced in magnitude in patients with schizophrenia, particularly at 40 Hz. While the neural mechanisms responsible for ASSR generation and its perturbation in schizophrenia are unknown, it has been hypothesized that the GABAA receptor subtype may have an important role....

GABAA receptors are the major inhibitory transmitter receptors in the central nervous system. They are chloride ion channels that can be opened by g-aminobutyric acid (GABA) and are the targets of action of a variety of pharmacologically and clinically important drugs. GABAA receptors are composed of five subunits that can belong to different subunit classes. The existence of 19 different subun...

There are coflicting reports regarding the role of GABA in morphine analgesia. While-sorne investigators have reported that treatment with GABAA receptor agonist muscimol and GABA transaminase inhibitors potentiates morphine analgesia (2.4.6) others have reported antagonism of morphine analgesia (8.10). In view of these conflicting reports and since the analgesic profile 'of THIP, a GABAA recep...