Age-related changes in large-conductance calcium-activated potassium channels in mammalian circadian clock neurons.
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 Ca(2+)-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 Ca(2+) concentration ([Ca(2+)]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 [Ca(2+)]i. These data suggest that reduced BK current increases [Ca(2+)]i by altering the action potential waveform, possibly contributing to the observed age-related phenotype.
Laboratory of Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Sahar
S
Farajnia
Laboratory of Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Johanna H
JH
Meijer
Laboratory of Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: s.michel@lumc.nl.
Stephan
S
Michel
D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics* / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics*; D004553:Electric Conductivity; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D013493:Suprachiasmatic Nucleus / Q000473:pathology* / Q000503:physiopathology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium
Action potential; Afterhyperpolarization; Aging; Calcium; Potassium channels; Suprachiasmatic nucleus