Isoflurane Modulates Hippocampal Cornu Ammonis Pyramidal Neuron Excitability by Inhibition of Both Transient and Persistent Sodium Currents in Mice

Overview

Journal Anesthesiology

Specialty Anesthesiology

Date 2019 Jun 6

PMID 31166240

Citations 10

Authors

Wenling Zhao

Mingyue Zhang

Jin Liu

Peng Liang

Rurong Wang

Hugh C Hemmings

Cheng Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Volatile anesthetics inhibit presynaptic voltage-gated sodium channels to reduce neurotransmitter release, but their effects on excitatory neuron excitability by sodium current inhibition are unclear. The authors hypothesized that inhibition of transient and persistent neuronal sodium currents by the volatile anesthetic isoflurane contributes to reduced hippocampal pyramidal neuron excitability.

Methods: Whole-cell patch-clamp recordings of sodium currents of hippocampal cornu ammonis pyramidal neurons were performed in acute mouse brain slices. The actions of isoflurane on both transient and persistent sodium currents were analyzed at clinically relevant concentrations of isoflurane.

Results: The median inhibitory concentration of isoflurane for inhibition of transient sodium currents was 1.0 ± 0.3 mM (~3.7 minimum alveolar concentration [MAC]) from a physiologic holding potential of -70 mV. Currents from a hyperpolarized holding potential of -120 mV were minimally inhibited (median inhibitory concentration = 3.6 ± 0.7 mM, ~13.3 MAC). Isoflurane (0.55 mM; ~2 MAC) shifted the voltage-dependence of steady-state inactivation by -6.5 ± 1.0 mV (n = 11, P < 0.0001), but did not affect the voltage-dependence of activation. Isoflurane increased the time constant for sodium channel recovery from 7.5 ± 0.6 to 12.7 ± 1.3 ms (n = 13, P < 0.001). Isoflurane also reduced persistent sodium current density (median inhibitory concentration = 0.4 ± 0.1 mM, ~1.5 MAC) and resurgent currents. Isoflurane (0.55 mM; ~2 MAC) reduced action potential amplitude, and hyperpolarized resting membrane potential from -54.6 ± 2.3 to -58.7 ± 2.1 mV (n = 16, P = 0.001).

Conclusions: Isoflurane at clinically relevant concentrations inhibits both transient and persistent sodium currents in hippocampal cornu ammonis pyramidal neurons. These mechanisms may contribute to reductions in both hippocampal neuron excitability and synaptic neurotransmission.

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References

Taheri S, Halsey M, Liu J, Eger 2nd E, Koblin D, Laster M . What solvent best represents the site of action of inhaled anesthetics in humans, rats, and dogs?. Anesth Analg. 1991; 72(5):627-34. DOI: 10.1213/00000539-199105000-00010. View

Westphalen R, Hemmings Jr H . Volatile anesthetic effects on glutamate versus GABA release from isolated rat cortical nerve terminals: basal release. J Pharmacol Exp Ther. 2005; 316(1):208-15. DOI: 10.1124/jpet.105.090647. View

Herold K, Hemmings Jr H . Sodium channels as targets for volatile anesthetics. Front Pharmacol. 2012; 3:50. PMC: 3316150. DOI: 10.3389/fphar.2012.00050. View

Hotson J, Prince D, Schwartzkroin P . Anomalous inward rectification in hippocampal neurons. J Neurophysiol. 1979; 42(3):889-95. DOI: 10.1152/jn.1979.42.3.889. View

Sittl R, Lampert A, Huth T, Schuy E, Link A, Fleckenstein J . Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl Acad Sci U S A. 2012; 109(17):6704-9. PMC: 3340057. DOI: 10.1073/pnas.1118058109. View

MacIver M, Kendig J . Anesthetic effects on resting membrane potential are voltage-dependent and agent-specific. Anesthesiology. 1991; 74(1):83-8. DOI: 10.1097/00000542-199101000-00014. View

Herold K, Nau C, Ouyang W, Hemmings Jr H . Isoflurane inhibits the tetrodotoxin-resistant voltage-gated sodium channel Nav1.8. Anesthesiology. 2009; 111(3):591-9. PMC: 2756082. DOI: 10.1097/ALN.0b013e3181af64d4. View

Tokuno H, Kocsis J, Waxman S . Noninactivating, tetrodotoxin-sensitive Na+ conductance in peripheral axons. Muscle Nerve. 2003; 28(2):212-7. DOI: 10.1002/mus.10421. View

CRILL W . Persistent sodium current in mammalian central neurons. Annu Rev Physiol. 1996; 58:349-62. DOI: 10.1146/annurev.ph.58.030196.002025. View

10.

Lunko O, Isaev D, Maximyuk O, Ivanchick G, Sydorenko V, Krishtal O . Persistent sodium current properties in hippocampal CA1 pyramidal neurons of young and adult rats. Neurosci Lett. 2013; 559:30-3. DOI: 10.1016/j.neulet.2013.11.035. View

11.

Moser M, Moser E . Functional differentiation in the hippocampus. Hippocampus. 1999; 8(6):608-19. DOI: 10.1002/(SICI)1098-1063(1998)8:6<608::AID-HIPO3>3.0.CO;2-7. View

12.

Yamada-Hanff J, Bean B . Activation of Ih and TTX-sensitive sodium current at subthreshold voltages during CA1 pyramidal neuron firing. J Neurophysiol. 2015; 114(4):2376-89. PMC: 4620139. DOI: 10.1152/jn.00489.2015. View

13.

Suzuki A, Aizawa K, Gassmayr S, Bosnjak Z, Kwok W . Biphasic effects of isoflurane on the cardiac action potential: an ionic basis for anesthetic-induced changes in cardiac electrophysiology. Anesthesiology. 2002; 97(5):1209-17. DOI: 10.1097/00000542-200211000-00026. View

14.

Raimondo J, Richards B, Woodin M . Neuronal chloride and excitability - the big impact of small changes. Curr Opin Neurobiol. 2016; 43:35-42. DOI: 10.1016/j.conb.2016.11.012. View

15.

Westphalen R, Desai K, Hemmings Jr H . Presynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane. Br J Anaesth. 2012; 110(4):592-9. PMC: 3600942. DOI: 10.1093/bja/aes448. View

16.

Zhong T, Qing Q, Yang Y, Zou W, Ye Z, Yan J . Repression of contexual fear memory induced by isoflurane is accompanied by reduction in histone acetylation and rescued by sodium butyrate. Br J Anaesth. 2014; 113(4):634-43. DOI: 10.1093/bja/aeu184. View

17.

Wu X, Sun J, Evers A, Crowder M, Wu L . Isoflurane inhibits transmitter release and the presynaptic action potential. Anesthesiology. 2004; 100(3):663-70. DOI: 10.1097/00000542-200403000-00029. View

18.

Astman N, Gutnick M, Fleidervish I . Persistent sodium current in layer 5 neocortical neurons is primarily generated in the proximal axon. J Neurosci. 2006; 26(13):3465-73. PMC: 6673860. DOI: 10.1523/JNEUROSCI.4907-05.2006. View

19.

Bi S, Deng C, Zhou T, Guan Z, Li L, Li H . Remifentanil-sevoflurane interaction models of circulatory response to laryngoscopy and circulatory depression. Br J Anaesth. 2013; 110(5):729-40. DOI: 10.1093/bja/aes504. View

20.

Storm J . Potassium currents in hippocampal pyramidal cells. Prog Brain Res. 1990; 83:161-87. DOI: 10.1016/s0079-6123(08)61248-0. View