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Kv4 channels underlie A-currents with highly variable inactivation time courses but homogeneous other gating properties in the nucleus tractus solitarii

  • Neuroscience
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Abstract

In the nucleus of the tractus solitarii (NTS), a large proportion of neurones express transient A-type potassium currents (I KA) having deep influence on the fidelity of the synaptic transmission of the visceral primary afferent inputs to second-order neurones. Up to now, the strong impact of I KA within the NTS was considered to result exclusively from its variation in amplitude, and its molecular correlate(s) remained unknown. In order to identify which Kv channels underlie I KA in NTS neurones, the gating properties and the pharmacology of this current were determined using whole cell patch clamp recordings in slices. Complementary information was brought by immunohistochemistry. Strikingly, two neurone subpopulations characterized by fast or slow inactivation time courses (respectively about 50 and 200 ms) were discriminated. Both characteristics matched those of the Kv4 channel subfamily. The other gating properties, also matching the Kv4 channel ones, were homogeneous through the NTS. The activation and inactivation occurred at membrane potentials around the threshold for generating action potentials, and the time course of recovery from inactivation was rapid. Pharmacologically, I KA in NTS neurones was found to be resistant to tetraethylammonium (TEA), sea anemone toxin blood-depressing substance (BDS) and dendrotoxin (DTX), whereas Androctonus mauretanicus mauretanicus toxin 3 (AmmTX3), a scorpion toxin of the α-KTX 15 family that has been shown to block all the members of the Kv4 family, inhibited 80 % of I KA irrespectively of its inactivation time course. Finally, immunohistochemistry data suggested that, among the Kv4 channel subfamily, Kv4.3 is the prevalent subunit expressed in the NTS.

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Acknowledgments

This work was supported by Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Agence De l’Environnement et de la Maîtrise de l‘Energie and Région Provence-Alpes-Côte d’Azur (ADEME/Région PACA, fellowship to LS).

We are grateful to Jean-Pierre Kessler for performing immunohistochemical experiments. We also thank Dr. Brigitte Céard for her technical assistance in the production of the toxin AmmTX3.

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Authors and Affiliations

  1. Faculté de Médecine, Aix Marseille Université, CNRS, CRN2M, UMR 7286, Bd. Pierre Dramard, 13444, Marseille Cedex 15, France

    Caroline Strube, Layal Saliba, Estelle Moubarak, Virginie Penalba, Marie-France Martin-Eauclaire, Fabien Tell & Nadine Clerc

  2. Institut d’Education Physique et Sportive, Université Antonine Hadath-Baabda, Beirut, Lebanon

    Layal Saliba

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  1. Caroline Strube
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  2. Layal Saliba
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Correspondence to Nadine Clerc.

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Strube, C., Saliba, L., Moubarak, E. et al. Kv4 channels underlie A-currents with highly variable inactivation time courses but homogeneous other gating properties in the nucleus tractus solitarii. Pflugers Arch - Eur J Physiol 467, 789–803 (2015). https://doi.org/10.1007/s00424-014-1533-z

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