Benzodiazepines modulate GABAA receptors by reducing a gamma-subunit-mediated inhibition of GABA sensitivity

نویسندگان

  • Igor Baburin
  • Sophia Khom
  • Eugen Timin
  • Annette Hohaus
  • Werner Sieghart
  • Steffen Hering
چکیده

Background Heterologous expression of α1, β2 and γ2S(γ1) subunits produces a mixed population of GABAA receptors containing α1β2 or α1β2γ2S(γ1) subunits. GABA sensitivity (lower in receptors containing γ1 or γ2S subunits) and the potentiation of GABA-activated chloride currents (IGABA) by benzodiazepines (BZDs) are dependent on γ2S(γ1) incorporation [1]. A variable γ subunit incorporation may affect the estimation of IGABA potentiation by BZDs. We propose an approach for estimation of BZD efficiency that accounts for a mixed population of α1β2 and α1β2γ2S(γ1) receptors.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Structural Analysis and Binding Modes of Benzodiazepines with Modeled GABAA Receptor Subunit Gamma-2

Activation of chloride gated GABAA receptors regulates the excitatory transmission in the epileptic brain. Positive allosteric modulation of these receptors via distinct recognition sites is the therapeutic mechanism of antiepileptic agents which prevents the hyperexcitability associated with epilepsy. These distinct sites are based on subunit composition which determines binding of various dru...

متن کامل

Molecular basis for the GABAA receptor-mediated tonic inhibition in rat somatosensory cortex.

Fast inhibitory synaptic transmission is primarily mediated by synaptically released gamma-aminobutyric acid (GABA) acting on postsynaptic GABA(A) receptors. GABA acting on GABA(A) receptors produces not only phasic but also tonic inhibitions by persistent activation of extrasynaptic receptors. However, the mechanistic characteristics of tonic inhibition in the neocortex are not well-understood...

متن کامل

Diabetes induces GABA receptor plasticity in murine vagal motor neurons.

Autonomic dysregulation accompanies type-1 diabetes, and synaptic regulation of parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV) is altered after chronic hyperglycemia/hypoinsulinemia. Tonic gamma-aminobutyric acid A (GABAA) inhibition prominently regulates DMV neuron activity, which contributes to autonomic control of energy homeostasis. This study inv...

متن کامل

P145: The Role of γ-Aminobutyric Acid Receptor in The Social Anxiety Disorder

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...

متن کامل

Assembly and Heterogeneity of GABAA Receptors

The vast majority of inhibitory neurotransmission in the brain is mediated by γ-aminobutyric acid (GABA). It has been detected in approximately 30% of all synapses and acts via ionotropic GABAA receptors, which mediate fast inhibitory neurotransmission, and metabotropic GABAB receptors, which mediate slower inhibitory effects. GABAA receptors (GABAARs) are chloride channels belonging to the Cys...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2009