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Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurones

Published online by Cambridge University Press:  16 August 2006

M. E. Bräu  and
J. R. Elliott
M. E. Bräu
Affiliation:
Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, United Kingdom Present address: Abteilung Anaesthesiologie und Operative Intensivmedizin, Rudolf-Buchheim-Strasse 7, D-35392 Giessen, Germany
J. R. Elliott
Affiliation:
Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, United Kingdom
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Abstract

Besides the fast tetrodotoxin-sensitive Na+ current, small dorsal root ganglion neurones of rats also possess a slower tetrodotoxin-resistant Na+ current. The blocking effect of commonly used local anaesthetics upon the tetrodotoxin-resistant Na+ current was investigated in the present paper. Dorsal root ganglia were dissected from adult rats and cells were enzymatically isolated. The whole-cell patch clamp technique was then used to measure inward Na+ currents of small dorsal root ganglion neurones. Externally applied local anaesthetics reversibly blocked the tetrodotoxin-resistant Na+ current in a dose-dependent manner. Half-maximal blocking concentrations for tonic block were: lignocaine, 326 μm; prilocaine, 253 μm; mepivacaine, 166 μm; etidocaine, 196 μm bupivacaine, 57 μm procaine, 518 μm benzocaine, 489 μm; tetracaine, 21 μm; and dibucaine, 23 μm. Blocking of the current by lignocaine was independent of temperature. The quaternary lignocaine derivative QX-314 did not have any effect upon the tetrodotoxin-resistant Na+ current when applied externally. High concentrations of tetrodotoxin also blocked the tetrodotoxin-resistant Na+ current with a half-maximal blocking concentration of 115 μm. The block by high tetrodotoxin concentrations did not compete with the lignocaine block, suggesting that there were two independent blocking mechanisms for the two substances. The tetrodotoxin-resistant Na+ currents also showed a marked sensitivity to phasic (use-dependent) block by local anaesthetics.

Keywords

TTX-resistant Na+ channellocal anaestheticsdorsal root ganglionpatch clamp
Type
Pharmacological Study
Information
European Journal of Anaesthesiology , Volume 15 , Issue 1 , January 1998 , pp. 80 - 88
Copyright
1998 European Society of Anaesthesiology

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