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Acute temperature sensitivity in optic nerve axons explained by an electrogenic membrane potential

  • Neuroscience
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Classical work in squid axon reports resting membrane potential is independent of temperature, but our findings suggest that this is not the case for axons in mammalian optic nerve. Refractory period duration changes over 10 times between 37 °C and room temperature, and afterpotential polarity is also acutely temperature sensitive, inconsistent with changes in temperature impacting nerve function only through altered rates of ion channel gating kinetics. Our evidence suggests that the membrane potential is enhanced by warming, an effect reduced by exposure to ouabain. The temperature dependence can be explained if axonal Na+/K+ ATPase continuously expels Na+ ions that enter axons largely electroneutrally, thereby adding a substantial electrogenic component to the membrane potential. Block of the Na+ transporter NKCC1 with bumetanide increases refractoriness, like depolarization, indicating that this is a probable route by which Na+ enters, raising the expectation that the rate of electroneutral Na+ influx increases with temperature and suggesting a temperature-dependent transmembrane Na+ cycle that contributes to membrane potential.

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Abbreviations

QTRAC:

A computerized threshold-tracking programme available from Digitimer Ltd

ATX-II:

47 Amino acid peptidyl toxin from sea anemone, Anemonia sulcata

HEPES:

2-[4-(2-Hydroxyethyl)piperazin-1-yl]ethanesulfonic acid

NKCC1:

Bumetanide-sensitive Na-K-2Cl co-transporter

NHE, NHE1:

Na-H ion exchanger

DAP:

Depolarizing afterpotential

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Acknowledgments

We acknowledge the support of the MS society (MDB), Barts and the London MSc programme in Translational Neuroscience (GA), and a Rod Flower Scholarship (TAC, JM). We thank Christopher Pendleton for the technical assistance and Peter Reeh, Hugh Bostock, and Monica Calado-Marta for the comments on previous versions of this manuscript.

Compliance with ethical standards statement

Procedures for isolation of ex vivo animal tissue were in accordance with Home Office UK regulations.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Neuroscience and Trauma Centre, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, 4 Newark Street, London, E12AT, UK

    Tom A. Coates, Oscar Woolnough, Joseph M. Masters, Gulsum Asadova, Charmilie Chandrakumar & Mark D. Baker

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  1. Tom A. Coates
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  2. Oscar Woolnough
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Correspondence to Mark D. Baker.

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Coates, T.A., Woolnough, O., Masters, J.M. et al. Acute temperature sensitivity in optic nerve axons explained by an electrogenic membrane potential. Pflugers Arch - Eur J Physiol 467, 2337–2349 (2015). https://doi.org/10.1007/s00424-015-1696-2

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