Stoichiometry of GABA-receptor interactions: GABA modulates the glycine-receptor interaction allosterically in a vertebrate neuron.
1. Measurement of steady-state conductance changes provides a reliable method for determination of transmitter-receptor stoichiometry in general and for GABA and its receptor interactions in particular. Log-log plotting of steady-state conductance changes as a function of decreasing transmitter concentration gives the molecularity of the interaction as a limiting slope. 2. Suitable measurements of GABA action in locust muscle show a molecularity of 3 with strong positive cooperativity. One molecule of picrotoxin is sufficient to block this reaction. Kinetic studies reveal the presence of occult desensitization. Thermodynamic studies reveal strong negative heats of interaction compatible with conformational changes in a multi-subunit receptor. 3. Measurements in the lateral dendrite of the goldfish Mauthner cell reveal that glycine has a more powerful action than GABA. Both interactions, however, utilize 4 molecules of amino acid with strong positive cooperativity to activate its receptors. The receptors are apparently distinct and there appears to be a higher glycine-receptor density. 4. In addition to its action on its own receptor, GABA allosterically modulates the glycine-receptor interaction in the Mauthner cell by lowering the energy barrier for the binding of the first glycine molecule, thereby increasing the affinity of glycine for its receptor.
D000494:Allosteric Regulation; D000818:Animals; D004553:Electric Conductivity; D005998:Glycine / Q000378:metabolism*; D006110:Grasshoppers; D007700:Kinetics; D008433:Mathematics; D009132:Muscles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D013816:Thermodynamics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D005998:Glycine; D010852:Picrotoxin; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid