Complex blockade of TTX-resistant Na+ currents by lidocaine and bupivacaine reduce firing frequency in DRG neurons

Journal of Neurophysiology
Andreas M ScholzW Vogel

Abstract

Mechanisms of blockade of tetrodotoxin-resistant (TTXr) Na+ channels by local anesthetics in comparison with the sensitivity of tetrodotoxin-sensitive (TTXs) Na+ channels were studied by means of the patch-clamp technique in neurons of dorsal root ganglions (DRG) of rat. Half-maximum inhibitory concentration (IC50) for the tonic block of TTXr Na+ currents by lidocaine was 210 micromol/l, whereas TTXs Na+ currents showed five times lower IC50 of 42 micromol/l. Bupivacaine blocked TTXr and TTXs Na+ currents more potently with IC50 of 32 and 13 micromol/l, respectively. In the inactivated state, TTXr Na+ channel block by lidocaine showed higher sensitivities (IC50 = 60 micromol/l) than in the resting state underlying tonic blockade. The time constant tau1 of recovery of TTXr Na+ channels from inactivation at -80 mV was slowed from 2 to 5 ms after addition of 10 micromol/l bupivacaine, whereas the tau2 value of approximately 500 ms remained unchanged. The use-dependent block of TTXr Na+ channels led to a progressive reduction of current amplitudes with increasing frequency of stimulation, which was </=53% block at 20 Hz in 10 micromol/l bupivacaine and 81% in 100 micromol lidocaine. The functional importance of the use-dependent bl...Continue Reading

References

Oct 1, 1989·British Journal of Anaesthesia·J A WildsmithS Johnson
Nov 1, 1988·Pflügers Archiv : European journal of physiology·E Carbone, H D Lux
Aug 1, 1980·Pflügers Archiv : European journal of physiology·J Schmidtmayer, W Ulbricht
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
May 1, 1983·The Journal of General Physiology·B P BeanR W Tsien
Sep 1, 1993·Journal of Neurophysiology·A ScholzH Bostock
Mar 1, 1997·The European Journal of Neuroscience·M MadejaE J Speckmann

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Citations

May 30, 2001·Critical Care Medicine·K HirotaD G Lambert
Apr 28, 2001·British Journal of Pharmacology·M W HollmannM E Durieux
Mar 26, 2003·Anesthesia and Analgesia·Gertrud HaeselerMartin Leuwer
Jun 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Birgit T PriestWilliam J Martin
Jun 6, 2007·Australian Dental Journal·C Yu, P V Abbott
Apr 23, 2008·Molecular Pain·Songjiang LuoMichael A Henry
Apr 25, 2008·The Journal of Pharmacology and Experimental Therapeutics·Takafumi Horishita, R Adron Harris
Jul 15, 2009·The Journal of Physiology·Desdemona FrickerRichard Miles
Mar 12, 2010·Journal of Receptor and Signal Transduction Research·Mete OzcanSelim Kutlu
Oct 27, 2016·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Henri DubocMuriel Larauche
Apr 26, 2002·Anesthesia and Analgesia·Mattias CasuttAlain Borgeat
Jul 26, 2000·Anesthesiology·M W HollmannM E Durieux
Aug 1, 2002·The Journal of General Physiology·Chung-Chin KuoChi-Pan Hsieh
Nov 3, 2010·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Raymond Sinatra
Sep 16, 2011·Current Medical Research and Opinion·Charles Argoff
Oct 15, 2013·British Journal of Pharmacology·C BrenneisC J Woolf
Jun 22, 2000·Anesthesiology·S A IsaacsonJ Yang
Sep 2, 2000·Anesthesiology·M W Hollmann, M E Durieux
Aug 2, 2003·British Journal of Pharmacology·Ulrike BischoffAndrea Olschewski
Feb 24, 2004·The Journal of Pharmacology and Experimental Therapeutics·Munehiro Shiraishi, R Adron Harris
Aug 4, 2015·Regional Anesthesia and Pain Medicine·Xiaojia WangJin Liu

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