Afterhyperpolarization regulates firing rate in neurons of the suprachiasmatic nucleus

J Neurosci. 2003 Mar 1;23(5):1593-604. doi: 10.1523/JNEUROSCI.23-05-01593.2003.


Cluster I neurons of the suprachiasmatic nucleus (SCN), which are thought to be pacemakers supporting circadian activity, fire spontaneous action potentials that are followed by a monophasic afterhyperpolarization (AHP). Using a brain slice preparation, we have found that the AHP has a shorter duration in cells firing at higher frequency, consistent with circadian modulation of the AHP. The AHP is supported by at least three subtypes of K(Ca) channels, including apamin-sensitive channels, iberiotoxin-sensitive channels, and channels that are insensitive to both of these antagonists. The latter K(Ca) channel subtype is involved in rate-dependent regulation of the AHP. Voltage-clamped, whole-cell Ca(2+) channel currents recorded from SCN neurons were dissected pharmacologically, revealing all of the major high-voltage activated subtypes: L-, N-, P/Q-, and R-type Ca(2+) channel currents. Application of Ca(2+) channel antagonists to spontaneously firing neurons indicated that predominantly L- and R-type currents trigger the AHP. Our findings suggest that apamin- and iberiotoxin-insensitive K(Ca) channels are subject to diurnal modulation by the circadian clock and that this modulation either directly or indirectly leads to the expression of a circadian rhythm in spiking frequency.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Apamin / pharmacology
  • Biological Clocks / physiology
  • Cadmium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Circadian Rhythm / physiology
  • GABA Antagonists / pharmacology
  • In Vitro Techniques
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors
  • Potassium Channels, Calcium-Activated / metabolism
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / drug effects
  • Suprachiasmatic Nucleus / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Calcium Channel Blockers
  • Calcium Channels
  • GABA Antagonists
  • Peptides
  • Potassium Channels, Calcium-Activated
  • Cadmium
  • Apamin
  • iberiotoxin