Journal article

Publication year: 2005

Pages: 826-833

Journal: British Journal of Pharmacology

Volume number: 146

Issue number: 6

ISSN: 0007-1188

eISSN: 1476-5381

Open access status: Green

DOI Link: https://doi.org/10.1038/sj.bjp.0706385

Publisher: Wiley

Abstract: 

1 Ketamine shows, besides its general anaesthetic effect, a potent analgesic effect after spinal administration. We investigated the local anaesthetic-like action of ketamine and its enantiomers in Na+ and K+ channels and their functional consequences in dorsal horn neurones of laminae I-III, which are important neuronal structures for pain transmission receiving most of their primary sensory input from Ad and C fibres.

2 Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method, we studied action of ketamine on Na+ and voltage-activated K+ currents. The changes in repetitive firing behaviour of tonically firing neurones were investigated in current-clamp mode after application of ketamine.

3 Concentration-effect curves for the Na+ peak current revealed for tonic block half-maximal inhibiting concentrations ( IC50) of 128 mu M and 269 mu M for S( +) and R( -)- ketamine, respectively, showing a weak stereoselectivity. The block of Na+ current was use-dependent. The voltage-dependent K+ current ( K-DR) was also sensitive to ketamine with IC50 values of 266 mM and 196 mM for S( +) and R( -)- ketamine, respectively. Rapidly inactivating K+ currents ( K-A) were less sensitive to ketamine. The block of KDR channels led to an increase in action potential duration and, as a consequence, to lowering of the discharge frequency in the neurones.

4 We conclude that ketamine blocks Na+ and K-DR channels in superficial dorsal horn neurones of the lumbar spinal cord at clinically relevant concentrations for local, intrathecal application. Ketamine reduces the excitability of the neurones, which may play an important role in the complex mechanism of its action during spinal anaesthesia.

Harvard Citation style: Schnoebel, R., Wolff, M., Peters, S., Bräu, M., Scholz, A., Hempelmann, G., et al. (2005) Ketamine impairs excitability in superficial dorsal horn neurones by blocking sodium and voltage-gated potassium currents, British Journal of Pharmacology, 146(6), pp. 826-833. https://doi.org/10.1038/sj.bjp.0706385

APA Citation style: Schnoebel, R., Wolff, M., Peters, S., Bräu, M., Scholz, A., Hempelmann, G., Olschewski, H., & Olschewski, A. (2005). Ketamine impairs excitability in superficial dorsal horn neurones by blocking sodium and voltage-gated potassium currents. British Journal of Pharmacology. 146(6), 826-833. https://doi.org/10.1038/sj.bjp.0706385