A novel effect of zinc on the lobster muscle GABA receptor.
The effect of zinc (and copper) was investigated on the lobster muscle gamma-aminobutyric acid (GABA) receptor. Zinc (10 microns-1 mM) depressed the GABA-evoked conductance increase in a fully reversible manner by possibly binding to an imidazole group, suggested from pH titration studies on the evoked-chloride conductance. Other transition metal (period 4) divalent cations (up to 500 microM) were inactive in antagonizing GABA responses. Variation of external chloride or anion substitution did not perturb the zinc antagonism; however, decreasing the pH markedly decreased the potency of zinc. A possible explanation for these results is discussed. Although the zinc antagonism resembled that produced by picrotoxinin, combination of these two agents depressed the GABA dose--conductance curve in a manner expected for two antagonists acting on independent sites. The zinc binding site was also discrete from the GABA recognition site; the results are interpreted in terms of a distinct binding site for zinc and H+. The distortion of an agonist dose--response curve by formation of an inactive agonist-divalent cation complex is discussed; however, complexation of GABA did not explain the observed antagonism by zinc. By comparison, zinc had no effect on the GABA responses of rat ganglionic neurons. It is concluded that the zinc binding site, on lobster muscle, may be an important modulatory site for the GABA-evoked chloride conductance.
D000818:Animals; D002413:Cations, Divalent; D002712:Chlorides / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D008121:Nephropidae; D010852:Picrotoxin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D013329:Structure-Activity Relationship; D015032:Zinc / Q000494:pharmacology*
D002413:Cations, Divalent; D002712:Chlorides; D007473:Ion Channels; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D015032:Zinc