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

Neurobiol Aging. 2015 Jun;36(6):2176-83. doi: 10.1016/j.neurobiolaging.2014.12.040. Epub 2015 Jan 31.


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.

Keywords: Action potential; Afterhyperpolarization; Aging; Calcium; Potassium channels; Suprachiasmatic nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Action Potentials / physiology
  • Aging*
  • Animals
  • Calcium / metabolism
  • Circadian Clocks / genetics*
  • Circadian Clocks / physiology
  • Circadian Rhythm / genetics*
  • Electric Conductivity*
  • Large-Conductance Calcium-Activated Potassium Channels / physiology*
  • Membrane Potentials / genetics
  • Membrane Potentials / physiology
  • Mice, Inbred C57BL
  • Patch-Clamp Techniques
  • Suprachiasmatic Nucleus / pathology*
  • Suprachiasmatic Nucleus / physiopathology*


  • Large-Conductance Calcium-Activated Potassium Channels
  • Calcium