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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anesthetics, Local / pharmacology
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Animals
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Animals, Newborn
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Apamin / pharmacology
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Biological Clocks / physiology*
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Calcium / metabolism
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Calcium Channel Blockers / pharmacology
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Dendrites / drug effects
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Dendrites / metabolism
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Dendrites / physiology*
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Dendrites / ultrastructure
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Electric Stimulation / methods
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Electroencephalography / methods
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Enzyme Inhibitors / pharmacology
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Female
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In Vitro Techniques
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Indoles / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Potentials / radiation effects
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Mibefradil / pharmacology
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Mice
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Mice, Knockout
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Midline Thalamic Nuclei / cytology*
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Neurons / cytology
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Neurons / drug effects
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Neurons / radiation effects
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Patch-Clamp Techniques
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Sarcoplasmic Reticulum Calcium-Transporting ATPases / physiology*
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Sleep / physiology*
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Small-Conductance Calcium-Activated Potassium Channels / deficiency
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Small-Conductance Calcium-Activated Potassium Channels / physiology*
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Tetrodotoxin / pharmacology
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Walking / physiology
Substances
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Anesthetics, Local
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Calcium Channel Blockers
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Enzyme Inhibitors
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Indoles
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Kcnn1 protein, mouse
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Kcnn2 protein, mouse
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Small-Conductance Calcium-Activated Potassium Channels
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Apamin
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Mibefradil
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Tetrodotoxin
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
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Calcium
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cyclopiazonic acid