T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites

Lucius Cueni, Marco Canepari, Rafael Luján, Yann Emmenegger, Masahiko Watanabe, Chris T. Bond, Paul Franken, John P. Adelman, Anita Lüthi

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Abstract

T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.

Original languageEnglish (US)
Pages (from-to)683-692
Number of pages10
JournalNature Neuroscience
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2008

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ASJC Scopus subject areas

  • Neuroscience(all)

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Cueni, L., Canepari, M., Luján, R., Emmenegger, Y., Watanabe, M., Bond, C. T., Franken, P., Adelman, J. P., & Lüthi, A. (2008). T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites. Nature Neuroscience, 11(6), 683-692. https://doi.org/10.1038/nn.2124