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

Full 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.

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Author information

Author/s: Cueni, Lucius (L); Canepari, Marco (M); Luján, Rafael (R); Emmenegger, Yann (Y); Watanabe, Masahiko (M); Bond, Chris T (CT); Franken, Paul (P); Adelman, John P (JP); Lüthi, Anita (A);

Affiliation: Division of Pharmacology and Neurobiology, Biozentrum, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland.

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Nature neuroscience (Nat Neurosci), published in United States. (Language: eng)

Reference: 2008-Jun; vol 11 (issue 6) : pp 683-92

Dates: Created 2008/05/28; Completed 2008/08/13;

PMID: 18488023, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Anesthetics, Local - pharmacology
Animals
Animals, Newborn
Apamin - pharmacology
Biological Clocks - physiology
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Dendrites - drug effects; metabolism; physiology; ultrastructure
Electric Stimulation - methods
Electroencephalography - methods
Enzyme Inhibitors - pharmacology
Female
Indoles - pharmacology

Indoles - pharmacology
Membrane Potentials - drug effects; physiology; radiation effects
Mibefradil - pharmacology
Mice
Mice, Knockout
Midline Thalamic Nuclei - cytology
Neurons - cytology; drug effects; radiation effects
Patch-Clamp Techniques
Sarcoplasmic Reticulum Calcium-Transporting ATPases - physiology
Sleep - physiology
Small-Conductance Calcium-Activated Potassium Channels - deficiency; physiology
Tetrodotoxin - pharmacology
Walking - physiology

Associated Chemicals: Anesthetics, Local (0) ; Calcium Channel Blockers (0) ; Enzyme Inhibitors (0) ; Indoles (0) ; Kcnn1 protein, mouse (0) ; Kcnn2 protein, mouse (0) ; Small-Conductance Calcium-Activated Potassium Channels (0) ; Mibefradil (116644-53-2) ; cyclopiazonic acid (18172-33-3) ; Apamin (24345-16-2) ; Tetrodotoxin (4368-28-9) ; Calcium (7440-70-2) ; Sarcoplasmic Reticulum Calcium-Transporting ATPases (EC 3.6.3.8)

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