T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.
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.
Cueni
Lucius
L
Division of Pharmacology and Neurobiology, Biozentrum, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland.
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
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D020644:Midline Thalamic Nuclei / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D016138:Walking / Q000502:physiology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; C496895:Kcnn1 protein, mouse; C496898:Kcnn2 protein, mouse; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D020748:Mibefradil; D013779:Tetrodotoxin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid