Age-related changes in large-conductance calcium-activated potassium channels in mammalian circadian clock neurons

• Published in: Neurobiology of aging Vol. 36; no. 6; pp. 2176 - 2183
• Main Authors: Farajnia, Sahar, Meijer, Johanna H, Michel, Stephan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2015
• Subjects: Action potential; Action Potentials - genetics; Action Potentials - physiology; Afterhyperpolarization; Aging; Animals; Calcium; Calcium - metabolism; Circadian Clocks - genetics; Circadian Clocks - physiology; Circadian Rhythm - genetics; Electric Conductivity; Internal Medicine; Large-Conductance Calcium-Activated Potassium Channels - physiology; Membrane Potentials - genetics; Membrane Potentials - physiology; Mice, Inbred C57BL; Neurology; Patch-Clamp Techniques; Potassium channels; Suprachiasmatic nucleus; Suprachiasmatic Nucleus - pathology; Suprachiasmatic Nucleus - physiopathology; Suprachiasmatic nucleus; Aging; Action potential; Potassium channels; Afterhyperpolarization; Calcium
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2014.12.040

Abstract 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.