GABAergic synapses. Supramolecular organization and biochemical regulation.
Extraneurally released gamma-aminobutyric acid (GABA) interacts with specific recognition sites associated with proteins located in postsynaptic neuronal membranes that function as chloride (Cl-)ionophores. As a result of the interaction between GABA and the recognition sites, Cl- ionophores are opened causing an influx or an efflux of Cl-, depending on the values of the Cl- equilibrium potential and of the membrane potential. Hyperpolarization or depolarization will result from inward or outward Cl- fluxes, respectively. Independently of the change in conductivity elicited by GABA, this amino acid transmitter will reduce the effectiveness of the sodium ion (Na+) excitatory potential. In attempts to elucidate the molecular mechanism, whereby benzodiazepines facilitate the action of GABA on membrane conductance without changing the activity of Cl- or other ionophore, a basic protein (GABA-modulin, GM) has been isolated from rat brain which is similar in structure to the small molecular weight myelin basic protein, found in rodent brain. While GABA-modulin is located in synaptosomes, the small molecular weight myelin basic protein is located in the myelin fraction: more important, GABA-modulin inhibited the high affinity binding of GABA to crude synaptic membranes while the basic myelin protein did not. Also, amino acid composition and molecular weight differentiate the two proteins. The GABA-modulin can be phosphorylated with different stoichiometry by cyclic AMP-dependent protein kinase (4 mol PO4(-3)) or Ca2+-dependent protein kinase (1 mol PO4(-3)). Only cyclic AMP-dependent phosphorylation inhibited the action of GABA-modulin on GABA binding.
D000818:Animals; D002352:Carrier Proteins; D002712:Chlorides / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000502:physiology; D027361:Organic Anion Transporters; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D002352:Carrier Proteins; D002712:Chlorides; D050485:GABA Plasma Membrane Transport Proteins; D007476:Ionophores; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid