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A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones

  • Neuroscience
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Abstract

Non-adapting superior cervical ganglion (SCG) neurones with a clustering activity and sub-threshold membrane potential oscillations were occasionally recorded, suggesting the presence of a persistent sodium current (I NaP). The perforated-patch technique was used to establish its properties and physiological role. Voltage-clamp experiments demonstrated that all SCG cells have a TTX-sensitive I NaP activating at about −60 mV and with half-maximal activation at about −40 mV. The mean maximum I NaP amplitude was around −40 pA at −20 mV. Similar results were achieved when voltage steps or voltage ramps were used to construct the current–voltage relationships, and the general I NaP properties were comparable in mouse and rat SCG neurons. I NaP was inhibited by riluzole and valproate with an IC50 of 2.7 and 3.8 μM, respectively, while both drugs inhibited the transient sodium current (I NaT) with a corresponding IC50 of 34 and 150 μM. It is worth noting that 30 μM valproate inhibited the I NaP by 70% without affecting the I NaT. In current clamp, valproate (30 μM) hyperpolarised resting SCG membranes by about 2 mV and increased the injected current necessary to evoke an action potential by about 20 pA. Together, these results demonstrate for the first time that a persistent sodium current exists in the membrane of SCG sympathetic neurones which could allow them to oscillate in the sub-threshold range. This current also contributes to the resting membrane potential and increases cellular excitability, so that it is likely to play an important role in neuronal behaviour.

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Acknowledgements

This work was supported by a grant to J. A. Lamas from the Spanish Ministry of Education and Science (MEC- BFU2005-03494). E. S., M. R. and A. R. were Ph.D. students under the Galician Predoctoral, Spanish FPU and Spanish FPI programmes, respectively. S. J. R. was supported by a grant from Xunta de Galicia, PGIDIT (06PXIC310095PN). We wish to thank A. Senra and V. Domínguez for their technical assistance.

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Authors and Affiliations

  1. Section of Physiology, Department of Functional Biology, Faculty of Biology, University of Vigo, Lagoas-Marcosende, 36310, Vigo, Spain

    J. Antonio Lamas, Marcos Romero, Antonio Reboreda, Estela Sánchez & Sandro J. Ribeiro

  2. Faculty of Medicine, University of Extremo Sul Catarinense, Criciúma, Brazil

    Sandro J. Ribeiro

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  1. J. Antonio Lamas
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  2. Marcos Romero
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  3. Antonio Reboreda
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Correspondence to J. Antonio Lamas.

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J. A. L. and M. R. have contributed equally to this work.

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Lamas, J.A., Romero, M., Reboreda, A. et al. A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones. Pflugers Arch - Eur J Physiol 458, 589–599 (2009). https://doi.org/10.1007/s00424-009-0648-0

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  • DOI: https://doi.org/10.1007/s00424-009-0648-0

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