Abstract
Sevoflurane is widely used as a volatile anesthetic in clinical practice. However, its mechanism is still unclear. Recently, it has been reported that voltage-gated sodium channels have important roles in anesthetic mechanisms. Much attention has been paid to the effects of sevoflurane on voltage-dependent sodium channels. To elucidate this, we examined the effects of sevoflurane on Nav 1.8, Nav 1.4, and Nav 1.7 expressed in Xenopus oocytes. The effects of sevoflurane on Nav 1.8, Nav 1.4, and Nav 1.7 sodium channels were studied by an electrophysiology method using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. Sevoflurane at 1.0 mM inhibited the voltage-gated sodium channels Nav1.8, Nav1.4, and Nav1.7, but sevoflurane (0.5 mM) had little effect. This inhibitory effect of 1 mM sevoflurane was completely abolished by pretreatment with protein kinase C (PKC) inhibitor, bisindolylmaleimide I. Sevoflurane appears to have inhibitory effects on Nav1.8, Nav1.4, and Nav 1.7 by PKC pathways. However, these sodium channels might not be related to the clinical anesthetic effects of sevoflurane.
References
Lee SA, Choi JG, Zuo Z. Volatile anesthetics attenuate oxidative stress-reduced activity of glutamate transporter type 3. Anesth Analg. 2009;109:1506–10.
Hasegawa J, Takekoshi S, Nagata H, Osamura RY, Suzuki T. Sevoflurane stimulates MAP kinase signal transduction through the activation of PKC alpha and beta II in fetal rat cerebral cortex cultured neuron. Acta Histochem Cytochem. 2006;39:163–72.
Bouwman RA, van’t Hof FN, de Ruijter W, van Beek-Harmsen BJ, Musters RJ, de Lange JJ, Boer C. The mechanism of sevoflurane-induced cardioprotection is independent of the applied ischaemic stimulus in rat trabeculae. Br J Anaesth. 2006;97:307–14.
Yasui Y, Masaki E, Kato F. Sevoflurane directly excites locus coeruleus neurons of rats. Anesthesiology. 2007;107:992–1002.
Catterall WA, Goldin AL, Waxman SG. International Union of Pharmacology. XLVII. Nomenclature and structure–function relationships of voltage-gated sodium channels. Pharmacol Rev. 2005;57:397–409.
Ratnakumari L, Hemmings HC Jr. Inhibition of presynaptic sodium channels by halothane. Anesthesiology. 1998;88:1043–54.
Ouyang W, Wang G, Hemmings HC Jr. Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals. Mol Pharmacol. 2003;64:373–81.
Ratnakumari L, Vysotskaya TN, Duch DS, Hemmings HC Jr. Differential effects of anesthetic and nonanesthetic cyclobutanes on neuronal voltage-gated sodium channels. Anesthesiology. 2000;92:529–41.
Herold KF, Nau C, Ouyang W, Hemmings HC Jr. Isoflurane inhibits the tetrodotoxin-resistant voltage-gated sodium channel Nav1.8. Anesthesiology. 2009;111:591–9.
Shiraishi M, Harris RA. Effects of alcohols and anesthetics on recombinant voltage-gated Na+ channels. J Pharmacol Exp Ther. 2004;309:987–94.
Hemmings HC Jr. Sodium channels and the synaptic mechanisms of inhaled anaesthetics. Br J Anaesth. 2009;103:61–9.
Ouyang W, Herold KF, Hemmings HC Jr. Comparative effects of halogenated inhaled anesthetics on voltage-gated Na+ channel function. Anesthesiology. 2009;110:582–90.
Akopian AN, Sivilotti L, Wood JN. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature. 1996;379:257–62.
Djouhri L, Fang X, Okuse K, Wood JN, Berry CM, Lawson SN. The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons. J Physiol. 2003;550:739–52.
Gold MS, Weinreich D, Kim CS, Wang R, Treanor J, Porreca F, Lai J. Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain. J Neurosci. 2003;23:158–66.
Horishita T, Eger EI 2nd, Harris RA. The effects of volatile aromatic anesthetics on voltage-gated Na+ channels expressed in Xenopus oocytes. Anesth Analg. 2008;107:1579–86.
Horishita T, Harris RA. n-Alcohols inhibit voltage-gated Na+ channels expressed in Xenopus oocytes. J Pharmacol Exp Ther. 2008;326:270–7.
Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F, Duhamel L, Charon D, Kirilovsky J. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991;266:15771–81.
Minami K, Minami M, Harris RA. Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols and anesthetics. J Pharmacol Exp Ther. 1997;281(3):1136–43.
Minami K, Gereau RW IV, Minami M, Heinemann SF, Harris RA. Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes. Mol Pharmacol. 1998;53:148–56.
Frink EJ Jr, Malan TP, Atlas M, Dominguez LM, DiNardo JA, Brown BR Jr. Clinical comparison of sevoflurane and isoflurane in healthy patients. Anesth Analg. 1992;74:241–5.
Holaday DA, Smith FR. Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers. Anesthesiology. 1981;54:100–6.
Costa MR, Catterall WA. Phosphorylation of the alpha subunit of the sodium channel by protein kinase C. Cell Mol Neurobiol. 1984;4:291–7.
Vijayaragavan K, Boutjdir M, Chahine M. Modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by protein kinase A and protein kinase C. J Neurophysiol. 2004;91:1556–69.
Acknowledgments
This study was supported by a Grant-in-Aid for Scientific Research on Scientific Research (C) No. 20602019 and No. 23590282 (T. Y.), No. 23592263 (J. O.) and No. 23592264 (K. M.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
540_2011_1167_MOESM1_ESM.pptx
Supplemental Fig. 1. The protein kinase C pathway did not affect voltage-gated sodium channels. a Representative examples of the comparison of the pretreatment of bisindolylmaleimide I (GF109203X) and basal condition on Nav 1.8, Nav 1.4, and Nav 1.7. b Summary data for the pretreatment of GF109203X on peak inward current of voltage-gated sodium channels (Nav 1.8, Nav 1.4, and Nav 1.7.). The effects were expressed as rate of change (± SEM). (PPTX 178 kb)
About this article
Cite this article
Yokoyama, T., Minami, K., Sudo, Y. et al. Effects of sevoflurane on voltage-gated sodium channel Nav1.8, Nav1.7, and Nav1.4 expressed in Xenopus oocytes. J Anesth 25, 609–613 (2011). https://doi.org/10.1007/s00540-011-1167-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00540-011-1167-7