Targeting ligand-gated chloride channels for CNS inhibitory neurotransmission
GABAA receptors (Gamma-aminobutyric acid type A receptors) are ligand-gated chloride ion channels that mediate the primary inhibitory neurotransmission in the central nervous system (CNS). These receptors are pentamers comprising various combinations of α, β, γ, δ, ε, θ, π, and ρ subunits. The most common subtype in the human brain is α₁β₂γ₂. When GABA bind between the α and β subunits, the channel opens, allowing Cl⁻ ions to flow into the neuron. This leads to membrane hyperpolarization and the robust inhibition of neuronal firing.
GABAA receptor modulators (positive allosteric modulators or partial agonists) are used clinically to treat anxiety, insomnia, epilepsy and applied in anesthesia.
Major problems with classic non-selective modulators (like traditional benzodiazepines) include severe side effects such as sedation, tolerance, dependence, drowsiness, dizziness, confusion, and poor coordination. These side effects are particularly dangerous for elderly patients, who face a high risk of bone fractures due to unsteadiness.
ChanPharm staff members have significantly contributed to the discovery of a large number of new GABAA modulators derived from plant extracts (e.g., PubMed). A precise estimation of the GABA IC5-10 is a conditio sine qua non for the accurate determination of concentration-response data. Our assays enable discovery and validation of novel GABA receptor modulators, including characterization of their subtype specific activity.
SyncroPatch 384
Ligand-gated channel screening at scale.
The SyncroPatch 384 is a high-throughput automated patch clamp platform equipped for rapid fluidics and compound application, making it ideal for large-scale screening of GABAA modulators across multiple subunit combinations.
Best suited for: Primary screening, hit confirmation, and robust concentration-response profiling.
NANION TECHNOLOGIES HIGH THROUGHPUT
Patchliner
High-quality functional profiling with automation.
The Patchliner provides medium-throughput automated patch clamp recordings with rapid and highly precise compound application, essential for analyzing fast-desensitizing ligand-gated receptors like GABAA.
Best suited for: Secondary screening, precise IC5-10 estimations, and detailed subunit selectivity studies.
NANION TECHNOLOGIES MEDIUM THROUGHPUT
Manual Patch Clamp
Gold-standard electrophysiology.
Manual patch clamp paired with ultra-fast perfusion systems provides unmatched experimental control. It is highly valuable for deep mechanistic insights into the binding and kinetics of novel allosteric modulators.
Best suited for: Detailed receptor kinetics, complex pharmacological protocols, and validation of screening results.
CONVENTIONAL SYSTEMS GOLD STANDARD