The pathomechanism of amyotrophic lateral sclerosis (ALS) remains unclear. There is some evidence that excitotoxic cell death is involved in the degeneration of the motor nervous system, and that ligand-gated receptor channels play a role in the pathogenesis of the disease. Several electrophysiological and anatomical studies support the pathophysiological concept of an impaired inhibitory, name...

The inhibitory glycine receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on Glycine Receptors) is a member of Cys-loop superfamily transmitter-gated ion channels that includes zinc activated channels, GABAA, nicotinic acetylcholine and 5-HT3 receptors Zn2+- channels. expressed either homo-pentamer α subunits, or complex now thought to harbour 2α 3β subunits [33, 7], contain an intr...

GABA, the major inhibitory neurotransmitter in the mammalian brain, binds to GABAA receptors, which form chloride ion channels. The predicted structure of the GABAA receptor places a consensus phosphorylation site for cAMP-dependent protein kinase (PKA) on an intracellular domain of the channel. Phosphorylation by various protein kinases has been shown to alter the activity of certain ligand- a...

GABA is the main inhibitory neurotransmitter in the mammalian brain. The postsynaptic GABAA receptor/pore complex is presumed to be a pentamer typically composed of a combination of alpha, beta, and gamma subunits, although the stoichiometry remains controversial. We probed the stoichiometry of the GABAA receptor by site-directed mutagenesis of a conserved leucine (to serine) in the putative se...

Enhancement of the activation of GABAA receptors is a common feature of many sedative and hypnotic drugs, and it is probable that the GABAA receptor complex is a molecular target for these drugs in the mammalian central nervous system. We set out to elucidate the role of the two predominant ( 1 and 2) subunits of GABAA receptor in sedative drug action by studying mice lacking these two subunits...

Although three distinct subunits seem to be sufficient to form a functional pentameric GABAA receptor channel, cerebellar granule cells express nRNA for nine subunits. They receive GABAergic input from a relatively homogenous population of Golgi cells. It is not known whether all subunits are distributed similarly on the surface of granule cells or whether some of them have differential subcell...

Fluid accumulation is critical for lung distension and normal development. The multi-subunit γ-amino butyric acid type A receptors (GABAA) mainly act by mediating chloride ion (Cl-) fluxes. Since fetal lung actively secretes Cl--rich fluid, we investigated the role of GABAA receptors in fetal lung development. The physiological ligand, GABA, and its synthesizing enzyme, glutamic acid decarboxyl...

The inhibitory tone maintained throughout the central nervous system relies predominantly on the activity of neuronal GABAA (γ -aminobutyric acid type A) receptors. This receptor family comprises various subtypes that have unique regional distributions, but little is known about the role played by each subtype. The majority of the receptors contain a γ 2 subunit and are sensitive to modulation ...

A balance between excitatory and inhibitory neurotransmissions in brain is an essential factor for the proper function of the brain. The amino acid gamma-aminobutyric-acid (GABA) is considered as the major inhibitory neurotransmitter in brain. Thus, GABAergic neurons play a key role in regulating behavior. Previous data have revealed the complex subunit structural design for GABAA receptor chan...