Structural Mechanisms Underlying Benzodiazepine Modulation of the GABAA Receptor
نویسندگان
چکیده
منابع مشابه
Structural mechanisms underlying benzodiazepine modulation of the GABA(A) receptor.
Many clinically important drugs target ligand-gated ion channels; however, the mechanisms by which these drugs modulate channel function remain elusive. Benzodiazepines (BZDs), anesthetics, and barbiturates exert their CNS actions by binding to GABA(A) receptors and modulating their function. The structural mechanisms by which BZD binding is transduced to potentiation or inhibition of GABA-indu...
متن کاملContext Dependent Benzodiazepine Modulation of GABAA Receptor Opening Frequency
The anxiolytic, hypnotic, and anti-convulsant properties of benzodiazepines (BDZs) require modulation of distinct GABA(A) receptor alpha-subtypes. BDZ modulation of GABA(A) receptors is often described in terms of increased opening frequency, and contrasted with the increased open durations occurring with barbiturate modulation. Several studies spanning single channel, rapid kinetic, and whole ...
متن کاملMechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABAA Receptor Modulators?
Despite decades of basic and clinical research, our understanding of how benzodiazepines tend to lose their efficacy over time (tolerance) is at least incomplete. In appears that tolerance develops relatively quickly for the sedative and anticonvulsant actions of benzodiazepines, whereas tolerance to anxiolytic and amnesic effects probably does not develop at all. In light of this evidence, we ...
متن کاملAllosteric modulation by benzodiazepine receptor ligands of the GABAA receptor channel expressed in Xenopus oocytes.
Chick brain mRNA was isolated and injected into Xenopus oocytes. This led to the expression in the surface membrane of functional GABA-activated channels with properties reminiscent of vertebrate GABAA channels. The GABA-induced current was analyzed quantitatively under voltage-clamp conditions. Picrotoxin inhibited this current in a concentration-dependent manner with IC50 = 0.6 microM. The al...
متن کاملAgonist-, Antagonist-, and Benzodiazepine-Induced Structural Changes in the 1Met -Leu Region of the GABAA Receptor
The structural basis by which agonists, antagonists, and allosteric modulators exert their distinct actions on ligand-gated ion channels is poorly understood. We used the substituted cysteine accessibility method to probe the structure of the GABAA receptor in the presence of ligands that elicit different pharmacological effects. Residues in the 1Met -Leu region of the GABA binding site were in...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Neuroscience
سال: 2008
ISSN: 0270-6474,1529-2401
DOI: 10.1523/jneurosci.5727-07.2008