{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:35:11Z","timestamp":1791261311665,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chronic visceral pain is a key symptom of irritable bowel syndrome. Modulation of voltage\u2010gated calcium and potassium channels by G protein\u2010coupled receptors plays a key role in dampening nociceptive transmission. Both baclofen and the analgesic peptide \u03b1\u2010conotoxin Vc1.1 activate GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors (GABA\n                    <jats:sub>B<\/jats:sub>\n                    R), 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 calcium channels to reduce colonic nociception. Recent studies have also shown that GABA\n                    <jats:sub>B<\/jats:sub>\n                    R activation potentiates G\u2010protein\u2010coupled inwardly rectifying potassium (GIRK)\u20101\/2 channels in mammalian sensory afferent neurons. In this study, we investigated the expression of these ion channel targets in rodent and human dorsal root ganglion (DRG) neurons, including those innervating the colon. We examined how Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.2 and GIRK channel antagonists, as well as a GIRK channel activator, influence the passive and active electrical properties of adult mouse DRG neurons. We also assessed the effects of \u03b1\u2010conotoxin Vc1.1 on neuronal excitability in the presence of the selective Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.2 antagonist \u03c9\u2010conotoxin CVIE and the GIRK channel activator ML297. We further evaluated the impact of the GIRK channel antagonist tertiapin\u2010Q on excitability in mouse colonic DRGs and afferents and explored the role of hyperpolarization\u2010activated cyclic nucleotide\u2010gated (HCN) channels. Our findings demonstrate that both Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.2 inhibition and GIRK channel potentiation reduce excitability in mouse DRGs, likely mediating the antinociceptive effects of Vc1.1 and baclofen observed in vivo. However, GIRK channel potentiation appears to play only a limited role in modulating excitability in colon\u2010innervating DRGs and colonic afferents. These findings suggest that neurons innervating different body regions use distinct mechanisms to regulate excitability and nociceptive signalling.\n                  <\/jats:p>","DOI":"10.1113\/ep093318","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:41:12Z","timestamp":1764567672000},"page":"2026-2043","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["GABA\n                    <sub>B<\/sub>\n                    receptor\u2010mediated modulation of sensory neuron excitability: Roles of Ca\n                    <sub>V<\/sub>\n                    2.2, G\u2010protein\u2010coupled inwardly rectifying potassium (GIRK) channels, and hyperpolarisation\u2010activated cyclic nucleotide\u2010gated (HCN) channels in human and mouse nociception"],"prefix":"10.1113","volume":"111","author":[{"given":"Mariana","family":"Brizuela","sequence":"first","affiliation":[{"name":"Visceral Pain Research Group South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuja R.","family":"Bony","sequence":"additional","affiliation":[{"name":"Molecular Horizons\/Faculty of Science, Medicine and Health University of Wollongong  Wollongong New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Garcia\u2010Caraballo","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-2288","authenticated-orcid":false,"given":"David J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Molecular Horizons\/Faculty of Science, Medicine and Health University of Wollongong  Wollongong New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-2905","authenticated-orcid":false,"given":"Stuart M.","family":"Brierley","sequence":"additional","affiliation":[{"name":"Visceral Pain Research Group South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"},{"name":"Faculty of Health and Medical Sciences University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110255"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05829-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827dec42"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2020_130"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.109.058834"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0286-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012682399"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15690"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2014.103"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00331.2020"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00911"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3594-08.2008"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.22532"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002041"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201600297"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002314"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14115"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310971"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.08.017"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.131712"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i8.2091"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201000620"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00393-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn833"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4165"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001208"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206243"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273461"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1071\/CH23155"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114525"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121841"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00013.2019"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315631"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.170811"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21204"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306240"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-024-00593-4"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(00)00144-9"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP278148"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.1c00072"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36014-0"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.09.007"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202415333"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/jne.13122"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107792"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2006.07.023"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2015.05.009"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2834"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.05.012"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0136822100"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00158"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00135-8"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17976"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.08.061"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.09.003"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DO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