{"id":781,"date":"2026-04-15T13:14:18","date_gmt":"2026-04-15T13:14:18","guid":{"rendered":"https:\/\/citations.tools.bio-logic.fr\/?p=781"},"modified":"2026-04-15T13:14:18","modified_gmt":"2026-04-15T13:14:18","slug":"zn2-inhibition-of-recombinant-gabaa-receptors-an-allosteric-state%e2%80%90dependent-mechanism-determined-by-the-%ce%b3%e2%80%90subunit","status":"publish","type":"post","link":"https:\/\/citations.tools.bio-logic.fr\/?p=781","title":{"rendered":"Zn<sup>2+<\/sup> inhibition of recombinant GABA<sub>A<\/sub> receptors: an allosteric, state\u2010dependent mechanism determined by the \u03b3\u2010subunit"},"content":{"rendered":"<h4>DOI:<\/h4>\n<p><a href=\"https:\/\/doi.org\/10.1111\/j.1469-7793.1998.609bv.x\" target=\"_blank\" rel=\"noopener\">10.1111\/j.1469-7793.1998.609bv.x<\/a><\/p>\n<h4>Authors:<\/h4>\n<p>Kevin J. Gingrich, Paul M. Burkat<\/p>\n<h4>Abstract:<\/h4>\n<p>1. The gamma-subunit in recombinant gamma-aminobutyric acid (GABAA) receptors reduces the sensitivity of GABA-triggered Cl- currents to inhibition by Zn2+ and transforms the apparent mechanism of antagonism from non-competitive to competitive. To investigate underlying receptor function we studied Zn2- effects on macroscopic and single-channel currents of recombinant alpha 1 beta 2 and alpha 1 beta 2 gamma 2 receptors expressed heterologously in HEK-293 cells using the patch-clamp technique and rapid solution changes. 2. Zn2+ present for &gt; 60 s (constant) inhibited peak, GABA (5 microM)-triggered currents of alpha 1 beta 2 receptors in a concentration-dependent manner (inhibition equation parameters: concentration at half-amplitude (IC50) = 0.94 microM; slope related to Hill coefficient, S = 0.7) that was unaffected by GABA concentration. The gamma 2 subunit (alpha 1 beta 2 gamma 2 receptor) reduced Zn2+ sensitivity more than fiftyfold (IC50 = 51 microM, S = 0.86); increased GABA concentration (100 microM) antagonized inhibition by reducing apparent affinity (IC50 = 322 microM, S = 0.79). Zn2+ slowed macroscopic gating of alpha 1 beta 2 receptors by inducing a novel slow exponential component in the activation time course and suppressing a fast component of control desensitization. For alpha 1 beta 2 gamma 2 receptors, Zn2+ accelerated a fast component of apparent desensitization. 3. Zn2+ preincubations lasting up to 10 s markedly increased current depression and activation slowing of alpha 1 beta 2 receptors, but had little effect on currents from alpha 1 beta 2 gamma 2 receptors. 4. Steady-state fluctuation analysis of macroscopic alpha 1 beta 2 gamma 2 currents (n = 5) resulted in control (2 microM GABA) power density spectra that were fitted by a sum of two Lorentzian functions (relaxation times: 37 +\/- 5.6 and 1.41 +\/- 0.15 ms, means +\/- S.E.M.). Zn2+ (200 microM) reduced the total power almost sixfold and accelerated the slow (23 +\/- 2.8 ms, P &lt; 0.05) without altering the fast (1.40 +\/- 0.16 ms) relaxation time. The ratio (fast\/slow) of Lorentzian areas was increased by Zn2+ (control, 3.39 +\/- 0.55; Zn2+, 4.9 +\/- 0.37, P &lt; 0.05). 5. Zn2+ (500 microM) depression of previously activated current amplitudes (% control) for alpha 1 beta 2 gamma 2 receptors was independent of GABA concentration (5 microM, 13.2 +\/- 0.72%; 100 microM, 12.2 +\/- 2.9%, P &lt; 0.8, n = 5). Both onset and offset inhibition time courses were biexponential. Onset rates were enhanced by Zn2+ concentration. Inhibition onset was also biexponential for preactivated alpha 1 beta 2 receptors with current depression more than fourfold less sensitive (5 microM GABA, IC50 = 3.8 microM, S = 0.84) relative to that in constant Zn2+. 6. The results lead us to propose a general model of Zn2+ inhibition of GABAA receptors in which Zn2+ binds to a single extracellular site, induces allosteric receptor inhibition involving two non-conducting states, site affinity is state-dependent, and the features of state dependence are determined by the gamma-subunit.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>DOI: 10.1111\/j.1469-7793.1998.609bv.x Authors: Kevin J. Gingrich, Paul M. Burkat Abstract: 1. The gamma-subunit in recombinant gamma-aminobutyric acid (GABAA) receptors reduces the sensitivity of GABA-triggered Cl- currents to inhibition by Zn2+ and transforms the apparent mechanism of antagonism from non-competitive to competitive. To investigate underlying receptor function we studied Zn2- effects on macroscopic and single-channel currents [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[21],"tags":[],"class_list":["post-781","post","type-post","status-publish","format-standard","hentry","category-rsc-200"],"_links":{"self":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/781","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=781"}],"version-history":[{"count":0,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/781\/revisions"}],"wp:attachment":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=781"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=781"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=781"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}