期刊
NEUROBIOLOGY OF AGING
卷 36, 期 6, 页码 2176-2183出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.12.040
关键词
Suprachiasmatic nucleus; Aging; Action potential; Afterhyperpolarization; Calcium; Potassium channels
资金
- NWO/ZonMw grant [TOPGo 91210064]
Aging impairs the function of the suprachiasmatic nucleus (SCN, the central mammalian clock), leading to a decline in the circadian rhythm of many physiological processes, including sleep-wake rhythms. Recent studies have found evidence of age-related changes in the circadian regulation of potassium currents; these changes presumably lead to a decrease in the SCN's electrical rhythm amplitude. Current through large-conductance Ca2+-activated K+ (BK) channels promote rhythmicity in both SCN neuronal activity and behavior. In many neuron types, changes in BK activity are correlated with changes in intracellular Ca2+ concentration ([Ca2+](i)). We performed patch-clamp recordings of SCN neurons in aged mice and observed that the circadian modulation of BK channel activity was lost because of a reduction in BK currents during the night. This reduced current diminished the afterhyperpolarization, depolarized the resting membrane potential, widened the action potential, and increased [Ca2+](i). These data suggest that reduced BK current increases [Ca2+](i) by altering the action potential waveform, possibly contributing to the observed age-related phenotype. (C) 2015 Elsevier Inc. All rights reserved.
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