One of the challenges of getting started with a tool like TheBrain is that it’s a blank slate. In this review, we’ll take a closer look at what’s new and improved, and what it means to you from a business standpoint. Overdosing or taking multiple GABA modulating drugs can result in respiratory depression due to increased GABA signaling in the medulla of the brain stem.Several months ago, TheBrain Technologies introduced the latest version of its powerful mind mapping and knowledge visualization tool, TheBrain 8, which provides new ways for you to classify, organize and manipulate your information.įor this build, the developer has focused heavily on the user experience – helping you get started faster with templates, making it easier to apply tags and thought types, a new timeline view and all-around faster performance make TheBrain 8 a pleasure to work with.
Furthermore, ethanol and benzodiazepines exhibit cross-tolerance with one another due to their similar mechanism of action. Alcohol withdrawal is treated with GABA modulating drugs, such as benzodiazepines. Ethanol, one of the oldest and most widely-used psychoactive substances, also exerts effects on the GABA-A receptor. They are used in surgical anesthesia, the treatment of epilepsy, REM-sleep disorders, alcohol withdrawal, essential tremor, and muscle spasticity. Benzodiazepines are a drug class that exerts its effects by binding to the GABA-A receptor, resulting in increased chloride ion permeability by changing the frequency with which the chloride channels open. There are numerous uses for drugs that modulate GABA signaling. Medications that act on the GABA receptor are commonly used as therapeutic medications and substances of abuse, and it is unlikely that any physician, regardless of specialty, will not encounter clinical situations that involve GABA. Consequently, regardless of binding to GABA-A or GABA-B receptors, GABA serves an inhibitory function. The GABA-B receptor functions via a metabotropic G-protein coupled receptor which increases postsynaptic potassium conductance and decreases presynaptic calcium conductance, which consequently hyperpolarizes the postsynaptic cell and prevents the conduction of an action potential in the presynaptic cell. Consequently, the influx of negatively charged chloride ions hyperpolarizes the cell, inhibiting the creation of an action potential. The extracellular concentration of chloride is normally much higher than the intracellular concentration.
The GABA-A receptor is an ionotropic receptor that increases chloride ion conductance into the cell in the presence of GABA. GABA binds to two major post-synaptic receptors, the GABA-A and GABA-B receptors. It is degraded by GABA-transaminase into succinate semialdehyde which then enters the citric acid cycle. GABA can then be degraded extracellularly or taken back up into glia or the presynaptic cell. When an action potential reaches the presynaptic cell, voltage-gated calcium channels open and calcium binds to synaptobrevin, which results in the fusion of the vesicle with the plasma membrane and releases GABA into the synaptic cleft where it can bind with GABA receptors. SNARE complexes help dock the vesicles into the plasma membrane of the cell. After synthesis, it is loaded into synaptic vesicles by the vesicular inhibitory amino acid transporter. GABA is synthesized in the cytoplasm of the presynaptic neuron from the precursor glutamate by the enzyme glutamate decarboxylase, an enzyme which uses vitamin B6 (pyridoxine) as a cofactor.