{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:02:55Z","timestamp":1790132575612,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      The analgesic action of paracetamol involves K\n                      <jats:sub>V<\/jats:sub>\n                      7 channels, and its metabolite N\u2010acetyl\u2010p\u2010benzo quinone imine (NAPQI), a cysteine modifying reagent, was shown to increase currents through such channels in nociceptors. Modification of cysteine residues by N\u2010ethylmaleimide, H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      , or nitric oxide has been found to modulate currents through K\n                      <jats:sub>V<\/jats:sub>\n                      7 channels. The study aims to identify whether, and if so which, cysteine residues in neuronal K\n                      <jats:sub>V<\/jats:sub>\n                      7 channels might be responsible for the effects of NAPQI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      To address this question, we used a combination of perforated patch\u2010clamp recordings, site\u2010directed mutagenesis, and mass spectrometry applied to recombinant K\n                      <jats:sub>V<\/jats:sub>\n                      7.1 to K\n                      <jats:sub>V<\/jats:sub>\n                      7.5 channels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Currents through the cardiac subtype K\n                      <jats:sub>V<\/jats:sub>\n                      7.1 were reduced by NAPQI. Currents through all other subtypes were increased, either by an isolated shift of the channel voltage dependence to more negative values (K\n                      <jats:sub>V<\/jats:sub>\n                      7.3) or by such a shift combined with increased maximal current levels (K\n                      <jats:sub>V<\/jats:sub>\n                      7.2, K\n                      <jats:sub>V<\/jats:sub>\n                      7.4, K\n                      <jats:sub>V<\/jats:sub>\n                      7.5). A stretch of three cysteine residues in the S2\u2010S3 linker region of K\n                      <jats:sub>V<\/jats:sub>\n                      7.2 was necessary and sufficient to mediate these effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implication<\/jats:title>\n                    <jats:p>\n                      The paracetamol metabolite N\u2010acetyl\u2010p\u2010benzo quinone imine (NAPQI) modifies cysteine residues of K\n                      <jats:sub>V<\/jats:sub>\n                      7 subunits and reinforces channel gating in homomeric and heteromeric K\n                      <jats:sub>V<\/jats:sub>\n                      7.2 to K\n                      <jats:sub>V<\/jats:sub>\n                      7.5, but not in K\n                      <jats:sub>V<\/jats:sub>\n                      7.1 channels. In K\n                      <jats:sub>V<\/jats:sub>\n                      7.2, a triple cysteine motif located within the S2\u2010S3 linker region mediates this reinforcement that can be expected to reduce the excitability of nociceptors and to mediate antinociceptive actions of paracetamol.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16380","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T19:25:30Z","timestamp":1713986730000},"page":"2851-2868","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A triple cysteine motif as major determinant of the modulation of neuronal K\n                    <sub>V<\/sub>\n                    7 channels by the paracetamol metabolite N\u2010acetyl\u2010p\u2010benzo quinone imine"],"prefix":"10.1111","volume":"181","author":[{"given":"Sutirtha","family":"Ray","sequence":"first","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Luca","family":"Stampf","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Kudlacek","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Center for Physiology and Pharmacology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Won","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Center for Physiology and 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