Skip to main content
SpringerLink
Log in

Role of T-type Calcium Channels in Generating Hyperexcitatory Behaviors during Emergence from Sevoflurane Anesthesia in Neonatal Rats

  • Original Article
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

In the current study, we sought to investigate whether T-type Ca2+ channels (TCCs) in the brain are involved in generating post-anesthetic hyperexcitatory behaviors (PAHBs). We found that younger rat pups (postnatal days 9–11) had a higher incidence of PAHBs and higher PAHB scores than older pups (postnatal days 16–18) during emergence from sevoflurane anesthesia. The power spectrum of the theta oscillations (4 Hz–8 Hz) in the prefrontal cortex was significantly enhanced in younger pups when PAHBs occurred, while there were no significant changes in older pups. Both the power of theta oscillations and the level of PAHBs were significantly reduced by the administration of TCC inhibitors. Moreover, the sensitivity of TCCs in the medial dorsal thalamic nucleus to sevoflurane was found to increase with age by investigating the kinetic properties of TCCs in vitro. TCCs were activated by potentiated GABAergic depolarization with a sub-anesthetic dose of sevoflurane (1%). These data suggest that (1) TCCs in the brain contribute to the generation of PAHBs and the concomitant electroencephalographic changes; (2) the stronger inhibitory effect of sevoflurane contributes to the lack of PAHBs in older rats; and (3) the contribution of TCCs to PAHBs is not mediated by a direct effect of sevoflurane on TCCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Sakai EM, Connolly LA, Klauck JA. Inhalation anesthesiology and volatile liquid anesthetics: focus on isoflurane, desflurane, and sevoflurane. Pharmacotherapy 2005, 25: 1773–1788.

    Article  CAS  Google Scholar 

  2. Costi D, Cyna AM, Ahmed S, Stephens K, Strickland P, Ellwood J, et al. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. Cochrane Database Syst Rev 2014, 12: CD007084.

    Google Scholar 

  3. Moore AD, Anghelescu DL. Emergence delirium in pediatric anesthesia. Paediatr Drugs 2017, 19: 11–20.

    Article  Google Scholar 

  4. Veyckemans F. Excitation phenomena during sevoflurane anaesthesia in children. Curr Opin Anaesthesiol 2001, 14: 339–343.

    Article  CAS  Google Scholar 

  5. Vlajkovic GP, Sindjelic RP. Emergence delirium in children: many questions, few answers. Anesth Analg 2007, 104: 84–91.

    Article  Google Scholar 

  6. Kain ZN, Caldwell-Andrews AA, Weinberg ME, Mayes LC, Wang SM, Gaal D, et al. Sevoflurane versus halothane: postoperative maladaptive behavioral changes: a randomized, controlled trial. Anesthesiology 2005, 102: 720–726.

    Article  CAS  Google Scholar 

  7. Hauber JA, Davis PJ, Bendel LP, Martyn SV, McCarthy DL, Evans MC, et al. Dexmedetomidine as a rapid bolus for treatment and prophylactic prevention of emergence agitation in anesthetized children. Anesth Analg 2015, 121: 1308–1315.

    Article  CAS  Google Scholar 

  8. Aouad MT, Al-Alami AA, Nasr VG, Souki FG, Zbeidy RA, Siddik-Sayyid SM. The effect of low-dose remifentanil on responses to the endotracheal tube during emergence from general anesthesia. Anesth Analg 2009, 108: 1157–1160.

    Article  CAS  Google Scholar 

  9. Dalens BJ, Pinard AM, Letourneau DR, Albert NT, Truchon RJ. Prevention of emergence agitation after sevoflurane anesthesia for pediatric cerebral magnetic resonance imaging by small doses of ketamine or nalbuphine administered just before discontinuing anesthesia. Anesth Analg 2006, 102: 1056–1061.

    Article  CAS  Google Scholar 

  10. Lim BG, Shen FY, Kim YB, Kim WB, Kim YS, Han HC, et al. Possible role of GABAergic depolarization in neocortical neurons in generating hyperexcitatory behaviors during emergence from sevoflurane anesthesia in the rat. ASN Neuro 2014, 6: 127–136.

    Article  CAS  Google Scholar 

  11. Chemin J, Cazade M, Lory P. Modulation of T-type calcium channels by bioactive lipids. Pflug Arch 2014, 466: 689–700.

    Article  CAS  Google Scholar 

  12. Varma A, He J, Weissfeld L, Devaskar SU. Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats. Am J Physiol Regul Integr Comp Physiol 2003, 284: R1560–R1566.

    Article  CAS  Google Scholar 

  13. Shen FY, Chen ZY, Zhong W, Ma LQ, Chen C, Yang ZJ, et al. Alleviation of neuropathic pain by regulating T-type calcium channels in rat anterior cingulate cortex. Mol Pain 2015, 11: 8.

    Article  CAS  Google Scholar 

  14. Huang L, Keyser BM, Tagmose TM, Hansen JB, Taylor JT, Zhuang H, et al. NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2, 3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride]: a new selective inhibitor of T-type calcium channels. J Pharmacol Exp Ther 2004, 309: 193–199.

    Article  CAS  Google Scholar 

  15. Huguenard JR. Block of T-type Ca(2+) channels is an important action of succinimide antiabsence drugs. Epilepsy Curr 2002, 2: 49–52.

    Article  Google Scholar 

  16. [16] Contreras D. The role of T-channels in the generation of thalamocortical rhythms. CNS Neurol Disord Drug Targets 2006, 5: 571–585.

    Article  CAS  Google Scholar 

  17. van Wijngaarden JB, Zucca R, Finnigan S, Verschure PF. The impact of cortical lesions on thalamo-cortical network dynamics after acute ischaemic stroke: a combined experimental and theoretical study. PLoS Comput Biol 2016, 12: e1005048.

    Article  CAS  Google Scholar 

  18. Huguenard JR. Low-threshold calcium currents in central nervous system neurons. Annu Rev Physiol 1996, 58: 329–348.

    Article  CAS  Google Scholar 

  19. Bough KJ, Gudi K, Han FT, Rathod AH, Eagles DA. An anticonvulsant profile of the ketogenic diet in the rat. Epilepsy Res 2002, 50: 313–325.

    Article  CAS  Google Scholar 

  20. Martin JC, Liley DT, Harvey AS, Kuhlmann L, Sleigh JW, Davidson AJ. Alterations in the functional connectivity of frontal lobe networks preceding emergence delirium in children. Anesthesiology 2014, 121: 740–752.

    Article  CAS  Google Scholar 

  21. Constant I, Seeman R, Murat I. Sevoflurane and epileptiform EEG changes. Paediatr Anaesth 2005, 15: 266–274.

    Article  Google Scholar 

  22. Mohanram A, Kumar V, Iqbal Z, Markan S, Pagel PS. Repetitive generalized seizure-like activity during emergence from sevoflurane anesthesia. Can J Anaesth 2007, 54: 657–661.

    Article  Google Scholar 

  23. Llinas RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP. Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A 1999, 96: 15222–15227.

    Article  CAS  Google Scholar 

  24. Llinas RR, Steriade M. Bursting of thalamic neurons and states of vigilance. J Neurophysiol 2006, 95: 3297–3308.

    Article  Google Scholar 

  25. Wei H, Bonjean M, Petry HM, Sejnowski TJ, Bickford ME. Thalamic burst firing propensity: a comparison of the dorsal lateral geniculate and pulvinar nuclei in the tree shrew. J Neurosci 2011, 31: 17287–17299.

    Article  CAS  Google Scholar 

  26. Hull C, Isaacson JS, Scanziani M. Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs. J Neurosci 2009, 29: 9127–9136.

    Article  CAS  Google Scholar 

  27. Saalmann YB. Intralaminar and medial thalamic influence on cortical synchrony, information transmission and cognition. Front Syst Neurosci 2014, 8: 83.

    Article  Google Scholar 

  28. Kaila K, Price TJ, Payne JA, Puskarjov M, Voipio J. Cation-chloride cotransporters in neuronal development, plasticity and disease. Nat Rev Neurosci 2014, 15: 637–654.

    Article  CAS  Google Scholar 

  29. Aptel H, Hilaire C, Pieraut S, Boukhaddaoui H, Mallie S, Valmier J, et al. The Cav3.2/alpha1H T-type Ca2+ current is a molecular determinant of excitatory effects of GABA in adult sensory neurons. Mol Cell Neurosci 2007, 36: 293–303.

    Article  CAS  Google Scholar 

  30. Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev 2007, 87: 1215–1284.

    Article  CAS  Google Scholar 

  31. Song I, Savtchenko L, Semyanov A. Tonic excitation or inhibition is set by GABA(A) conductance in hippocampal interneurons. Nat Commun 2011, 2: 376.

    Article  CAS  Google Scholar 

  32. Lecker I, Yin Y, Wang DS, Orser BA. Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by alpha5GABAA receptor-preferring inverse agonists. Br J Anaesth 2013, 110 Suppl 1: i73–i81.

    Article  CAS  Google Scholar 

  33. Ries CR, Puil E. Mechanism of anesthesia revealed by shunting actions of isoflurane on thalamocortical neurons. J Neurophysiol 1999, 81: 1795–1801.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation, Beijing, People’s Republic of China (81671058 and 81730031 to YW and 81401089 to MD); the National Research Foundation of Korea grants funded by the Republic of Korea (2019R1I1A1A01057744 to YK); and the Foundation of Shanghai Municipal Science and Technology Commission (19ZR1407500 to FS).

Author information

Author notes

  1. Feng-Yan Shen, Byung-Gun Lim and Wen Wen have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Feng-Yan Shen, Yu Zhang, Li-Qing Ma, Meng Deng & Ying-Wei Wang

  2. Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, 08308, Korea

    Byung-Gun Lim

  3. Department of Anesthesiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China

    Wen Wen

  4. Department of Physiology and Neuroscience Research Institute, College of Medicine, Korea University, Seoul, 02841, Korea

    Yang In Kim & Young-Beom Kim

  5. Institute of Brain Functional Genomics, East China Normal University, Shanghai, 200062, China

    Bo Cao & Yue-Guang Si

Authors
  1. Feng-Yan Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Byung-Gun Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yue-Guang Si
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li-Qing Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Meng Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yang In Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Young-Beom Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ying-Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Young-Beom Kim or Ying-Wei Wang.

Ethics declarations

Conflict of interest

The authors claim that there are no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, FY., Lim, BG., Wen, W. et al. Role of T-type Calcium Channels in Generating Hyperexcitatory Behaviors during Emergence from Sevoflurane Anesthesia in Neonatal Rats. Neurosci. Bull. 36, 519–529 (2020). https://doi.org/10.1007/s12264-019-00461-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-019-00461-x

Keywords

Search

Navigation