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This article is part of the supplement: Seventeenth Annual Computational Neuroscience Meeting: CNS*2008

Open Access Poster presentation

Mathematical modeling of isoflurane action on lamprey spinal neurons

Tamara J Schlichter1*, Anne C Smith2, Steven L Jinks2 and Timothy J Lewis1

Author Affiliations

1 Department of Mathematics, University of California, Davis, CA, 95616, USA

2 Department of Anesthesiology and Pain Medicine, University of California, Davis, CA, 95616, USA

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BMC Neuroscience 2008, 9(Suppl 1):P26  doi:10.1186/1471-2202-9-S1-P26

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2202/9/S1/P26


Published:11 July 2008

© 2008 Schlichter et al; licensee BioMed Central Ltd.

Poster presentation

Anesthetics are believed to modulate activity of a variety of voltage-gated and ligand-gated ion channels. However, the exact biophysical mechanisms underlying anesthesia remain unclear [1]. Recent experimental evidence suggests that the volatile anesthetic isoflurane targets the TREK and TASK two-pore potassium conductances [2] and the persistent sodium conductance (Jinks et al. unpublished results). Furthermore, recent data indicate that volatile anesthetics produce immobility, a fundamental element of anesthesia, predominantly through direct action at the level of the spinal cord [3].

We use mathematical modeling and experiments on the lamprey spinal cord to study the effects of isoflurane on neuronal activity. Our experimental results on the disinhibited spinal cord preparation suggest that the excitatory interneurons of the CPG are the main target of isoflurane. As the anesthetic concentration increases, ventral root activity (assumed to be representative of the activity of spinal cord excitatory interneurons) transitions from bursting to silent. However, in some animals the activity transitions directly from bursting to silent where in others it transitions from bursting to a brief period of tonic firing before falling silent.

We incorporate the anesthetic-sensitive TREK, TASK and persistent sodium conductances into a preexisting detailed biophysical model of the lamprey excitatory interneuron [4], and a canonical bursting model [5]. We then perform a thorough bifurcation analysis on these models. Our results suggest that the anesthetic effects of TREK, TASK and persistent sodium currents alone are sufficient to account for the transition from bursting to silent, but are not sufficient to account for a robust transition from bursting to tonic to silent.

Acknowledgements

Graduate student was partially supported by NSF VIGRE Grant No. DMS-0135345

References

  1. Gottschalk A, Haney P: Computational aspects of anesthetic action in simple neural models.

    Anesthesiology 2003, 98:548-564. PubMed Abstract | Publisher Full Text OpenURL

  2. Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M: Inhalational anesthetics activate two-pore-domain background K+ channels.

    Nat Neurosci 1999, 2(5):422-426. PubMed Abstract | Publisher Full Text OpenURL

  3. Antognini JF, Schwartz K: Exaggerated anesthetic requirements in the preferentially anesthetized brain.

    Anesthesiology 1993, 79:1244-1249. PubMed Abstract OpenURL

  4. Brodin L, Traven HGC, Lansner A, Wallen P, Ekeberg O, Grillner S: Computer simulations of N-methyl-D-aspartate receptor-induced membrane properties in a neuron model.

    J Neurophysiol 1991, 66(2):473-484. PubMed Abstract | Publisher Full Text OpenURL

  5. Butera RJ, Rinzel J, Smith JC: Models of respiratory rhythm generation in the pre-Botzinger complex. I. bursting pacemaker neurons.

    J Neurophysiol 1999, 82:382-397. PubMed Abstract | Publisher Full Text OpenURL