{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:40:34Z","timestamp":1772160034716,"version":"3.50.1"},"reference-count":89,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1072113"],"award-info":[{"award-number":["APP1072113"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Activation of GIRK channels via G protein\u2010coupled GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptors has been shown to attenuate nociceptive transmission. The analgesic \u03b1\u2010conotoxin Vc1.1 activates GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptors resulting in inhibition of Ca\n                      <jats:sub>v<\/jats:sub>\n                      2.2 and Ca\n                      <jats:sub>v<\/jats:sub>\n                      2.3 channels in mammalian primary afferent neurons. Here, we investigated the effects of analgesic \u03b1\u2010conotoxins on recombinant and native GIRK\u2010mediated K\n                      <jats:sup>+<\/jats:sup>\n                      currents and on neuronal excitability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The effects of analgesic \u03b1\u2010conotoxins, Vc1.1, RgIA, and PeIA, were investigated on inwardly\u2010rectifying K\n                      <jats:sup>+<\/jats:sup>\n                      currents in HEK293T cells recombinantly co\u2010expressing either heteromeric human GIRK1\/2 or homomeric GIRK2 subunits, with GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptors. The effects of \u03b1\u2010conotoxin Vc1.1 and baclofen were studied on GIRK\u2010mediated K\n                      <jats:sup>+<\/jats:sup>\n                      currents and the passive and active electrical properties of adult mouse dorsal root ganglion neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Analgesic \u03b1\u2010conotoxins Vc1.1, RgIA, and PeIA potentiate inwardly\u2010rectifying K\n                      <jats:sup>+<\/jats:sup>\n                      currents in HEK293T cells recombinantly expressing human GIRK1\/2 channels and GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptors. GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor\u2010dependent GIRK channel potentiation by Vc1.1 and baclofen occurs via a pertussis toxin\u2010sensitive G protein and is inhibited by the selective GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor antagonist CGP 55845. In adult mouse dorsal root ganglion neurons, GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor\u2010dependent GIRK channel potentiation by Vc1.1 and baclofen hyperpolarizes the cell membrane potential and reduces excitability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      This is the first report of GIRK channel potentiation via allosteric \u03b1\u2010conotoxin Vc1.1\u2010GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor agonism, leading to decreased neuronal excitability. Such action potentially contributes to the analgesic effects of Vc1.1 and baclofen observed in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15690","type":"journal-article","created":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T04:23:37Z","timestamp":1633148617000},"page":"179-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Analgesic \u03b1\u2010conotoxins modulate native and recombinant GIRK1\/2 channels via activation of GABA\n                    <sub>B<\/sub>\n                    receptors and reduce neuroexcitability"],"prefix":"10.1111","volume":"179","author":[{"given":"Anuja R.","family":"Bony","sequence":"first","affiliation":[{"name":"Illawarra Health and Medical Research Institute (IHMRI) University of Wollongong  Wollongong NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2546-7913","authenticated-orcid":false,"given":"Jeffrey R.","family":"McArthur","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute (IHMRI) University of Wollongong  Wollongong NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-4532","authenticated-orcid":false,"given":"Rocio K.","family":"Finol\u2010Urdaneta","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute (IHMRI) University of Wollongong  Wollongong NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-2288","authenticated-orcid":false,"given":"David J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute (IHMRI) University of Wollongong  Wollongong NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00370"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/md16060208"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01781.x"},{"issue":"1","key":"e_1_2_12_5_1","first-page":"S27","article-title":"The Concise Guide to PHARMACOLOGY 2021\/22: G protein\u2010coupled receptors","volume":"178","author":"Alexander S. 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