{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:08:20Z","timestamp":1766156900695},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":2009,"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":[[2003,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Hyperpolarizing voltage steps evoke slowly activating inward currents in a variety of neurones and in cardiac cells. This hyperpolarization\u2010activated inward current (<jats:italic>I<\/jats:italic><jats:sub>h<\/jats:sub>) is thought to play a significant role in cell excitability, firing frequency, or in setting of the resting membrane potential in these cells. We studied the effects of lidocaine, mepivacaine, QX\u2010314 and bupivacaine as well as its enantiomers on <jats:italic>I<\/jats:italic><jats:sub>h<\/jats:sub> in the membrane of dorsal root ganglion neurones (DRG).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The patch\u2010clamp technique was applied to small dorsal root ganglion neurones identified in 200 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> thin slices of young rat DRGs. Under voltage\u2010clamp conditions, the whole\u2010cell <jats:italic>I<\/jats:italic><jats:sub>h<\/jats:sub> current was recorded in the presence of different concentrations of the local anaesthetics. In current\u2010clamp mode the resting membrane potential and the voltage response of DRG neurones to injected current pulses were investigated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>I<\/jats:italic><jats:sub>h<\/jats:sub> was reversibly blocked by bupivacaine, lidocaine and mepivacaine applied externally in clinically relevant concentrations. Concentration\u2013response curves gave half\u2010maximum inhibiting concentrations of 55, 99 and 190 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>, respectively. Bupivacaine block of the <jats:italic>I<\/jats:italic><jats:sub>h<\/jats:sub> current was not stereoselective. No significant effect was observed when QX\u2010314 was applied to the external surface of the membrane.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In current\u2010clamp experiments 60 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> bupivacaine slightly hyperpolarized the membrane. The membrane stimulation by low\u2010amplitude current pulses in the presence of bupivacaine showed an increase of the hyperpolarizing responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our findings suggest an important role of the <jats:italic>I<\/jats:italic><jats:sub>h<\/jats:sub>\u2010block by local anaesthetics in the complex mechanism of drug action during epidural and spinal anaesthesia.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>139<\/jats:bold>, 1273\u20131280. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705363\">10.1038\/sj.bjp.0705363<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705363","type":"journal-article","created":{"date-parts":[[2003,7,30]],"date-time":"2003-07-30T15:17:24Z","timestamp":1059578244000},"page":"1273-1280","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Local anaesthetics block hyperpolarization\u2010activated inward current in rat small dorsal root ganglion neurones"],"prefix":"10.1111","volume":"139","author":[{"given":"Ulrike","family":"Bischoff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E","family":"Br\u00e4u","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunter","family":"Hempelmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Olschewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"9","article-title":"Effect of glucose concentration in bupivacaine solutions on the distribution of local anesthetics in cerebrospinal fluid during spinal anesthesia","volume":"9","author":"BISCOPING J.","year":"1986","journal-title":"Reg. 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