{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T08:16:28Z","timestamp":1793607388590,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"2b","license":[{"start":{"date-parts":[[2011,8,28]],"date-time":"2011-08-28T00:00:00Z","timestamp":1314489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,9,2]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>The primary use of local anaesthetics is to prevent or relieve pain by reversibly preventing action potential propagation through the inhibition of voltage\u2010gated sodium channels. The tetrodotoxin\u2010sensitive voltage\u2010gated sodium channel subtype Na<jats:sub>v<\/jats:sub>1.7, abundantly expressed in pain\u2010sensing neurons, plays a crucial role in perception and transmission of painful stimuli and in inherited chronic pain syndromes. Understanding the interaction of lidocaine with Na<jats:sub>v<\/jats:sub>1.7 channels could provide valuable insight into the drug's action in alleviating pain in distinct patient populations. The aim of this study was to determine how lidocaine interacts with multiple inactivated conformations of Na<jats:sub>v<\/jats:sub>1.7 channels.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>We investigated the interactions of lidocaine with wild\u2010type Na<jats:sub>v<\/jats:sub>1.7 channels and a paroxysmal extreme pain disorder mutation (I1461T) that destabilizes fast inactivation. Whole cell patch clamp recordings were used to examine the activity of channels expressed in human embryonic kidney 293 cells.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>Depolarizing pulses that increased slow inactivation of Na<jats:sub>v<\/jats:sub>1.7 channels also reduced lidocaine inhibition. Lidocaine enhanced recovery of Na<jats:sub>v<\/jats:sub>1.7 channels from prolonged depolarizing pulses by decreasing slow inactivation. A paroxysmal extreme pain disorder mutation that destabilizes fast inactivation of Na<jats:sub>v<\/jats:sub>1.7 channels decreased lidocaine inhibition.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>Lidocaine decreased the transition of Na<jats:sub>v<\/jats:sub>1.7 channels to the slow inactivated state. The fast inactivation gate (domain III\u2013IV linker) is important for potentiating the interaction of lidocaine with the Na<jats:sub>v<\/jats:sub>1.7 channel.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01209.x","type":"journal-article","created":{"date-parts":[[2011,1,14]],"date-time":"2011-01-14T12:25:38Z","timestamp":1295007938000},"page":"719-730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Lidocaine reduces the transition to slow inactivation in Na<sub>v<\/sub>1.7 voltage\u2010gated sodium channels"],"prefix":"10.1111","volume":"164","author":[{"given":"Patrick L","family":"Sheets","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W","family":"Jarecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore 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