Use-dependent block of GABA-activated chloride channels in crayfish muscle fibers by picrate.
In crayfish muscle fibers studied with intracellular microelectrodes the protein-binding agent, picrate (2,4,6-trinitrophenolate; 10(-5)-2 X 10(-4) M) was found to have a specific and dose-dependent inhibitory effect on the chloride conductance activated by bath-applied gamma-aminobutyric acid (GABA). A kinetic analysis showed that picrate did not interfere with GABA binding to its receptor. The blocking action of picrate was not increased by lowering the extracellular Cl- concentration which indicates that picrate is not likely to bind to the ionic selectivity site of the postsynaptic Cl- channel. In fibers first exposed to picrate (1-2 X 10(-4) M) and then, in the continuous presence of this drug, to GABA (5 X 10(-4) M), the latter induced a transient increase in the chloride conductance with an apparent rate constant of decay of about 40 sec. It is tentatively suggested that the site of action of picrate is a positively charged amino acid residue that is exposed through the action of GABA and critically involved in the chemical gating of the postsynaptic chloride channel.
D000818:Animals; D003400:Astacoidea / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000378:metabolism*; D010851:Picrates / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D007473:Ion Channels; D010851:Picrates; D005680:gamma-Aminobutyric Acid; C005858:picric acid