Feng, Hua-Jun and Robert L. Macdonald. Proton modulation of 1 3 GABAA receptor channel gating and desensitization. J Neurophysiol 92: 1577–1585, 2004. First published May 19, 2004; 10.1152/jn.00285.2004. GABAA receptor currents are phasic and desensitizing, whereas GABAA receptor currents are tonic and have no fast desensitization. receptors are subsynaptic and mediate phasic inhibition, wherea...

The inhibitory neurotransmitter !-aminobutyric acid (GABA) has multiple receptors. In mammals, the GABAA receptor subtype is modulated by neurosteroids. However, whether steroid interaction with the GABAA receptor is unique to mammals or a conserved feature in vertebrates is unknown. Thus, neurosteroid modulation of the GABAA receptor was investigated in the brain of the bullfrog (Rana catesbei...

Both the serotonergic and the endocannabinoid system play a major role in mediating fear and anxiety. In the basolateral amygdala (BLA) it has been shown that the cannabinoid receptor 1 (CB1) is highly co-expressed with 5-HT3 receptors on GABAergic interneurons suggesting that 5-HT3 receptor activity modulates CB1-mediated effects on inhibitory synaptic transmission. In the present study, we in...

Classical benzodiazepine drugs are in wide clinical use as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. They act by enhancing the -aminobutyric acidA (GABAA) receptor function in the central nervous system. The pharmacological relevance of the multitude of structurally diverse GABAA receptor subtypes has only recently been identified. Based on an in vivo point mutation strateg...

GABAA receptors mediate fast phasic inhibitory postsynaptic potentials and participate in slower tonic extrasynaptic inhibition. Thy1alpha6 mice with ectopic forebrain expression of GABAA receptor alpha6 subunits exhibit increased extrasynaptic GABAA receptor-mediated background conductance and reduced synaptic GABAA receptor currents in hippocampal CA1 neurons [W. Wisden et al. (2002) Neuropha...

...........................................................................................viii Abbreviations used in text....................................................................xi CHAPTER 1: General Introduction.........................................................1 I. Cardiac Arrest and Cerebral Ischemia............................................1 II. The Cerebellum and Purkin...

Modulatory agents of gamma-aminobutyric acid type A (GABAA) receptors have been widely used for more than 40 years to treat anxiety, epilepsy, and sleep disorders; these drugs are generally safe, well tolerated, and effective. Recently, there has been a substantial growth in understanding of the mechanism of action of these drugs, which act at different sites on GABAA receptors. A variety of GA...

Social anxiety disorder (SAD) is the one of the most common anxiety disorders. Despite its high prevalence, the disorder is still considerably undiagnosed and untreated. The disease places a massive burden on patient’s lives, affecting not only their social interactions but also their educational and professional activities, thereby constituting a severe disability. γ-aminobutyric acid (GABA) s...

Changes in GABAergic inhibition occur during physiological processes, during response to drugs and in various pathologies. These changes can be achieved through direct allosteric modifications at the γ-amino butyric acid (GABA) type A (GABAA) receptor protein level, or by altering the synthesis, trafficking and stability of the receptor. Neurosteroids (NSs) and protein kinase C (PKC) are potent...

A developmental "switch" in chloride transporters occurs in most neurons resulting in GABAA mediated hyperpolarization in the adult. However, several neuronal cell subtypes maintain primarily depolarizing responses to GABAA receptor activation. Among this group are gonadotropin-releasing hormone-1 (GnRH) neurons, which control puberty and reproduction. NKCC1 is the primary chloride accumulator ...