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The Journal of Neuroscience, March 1, 2003, 23(5):1593
Afterhyperpolarization Regulates Firing Rate in Neurons of the Suprachiasmatic Nucleus
Robin K. Cloues and William A. Sather Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262
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 KCa channels, including apamin-sensitive channels, iberiotoxin-sensitive channels, and channels that are insensitive to both of these antagonists. The latter KCa channel subtype is involved in rate-dependent regulation of the AHP. Voltage-clamped, whole-cell Ca2+ 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 Ca2+ channel currents. Application of Ca2+ 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 KCa 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.
Key words: suprachiasmatic nucleus; calcium channel; calcium-activated potassium channel; action potential; spontaneous activity; afterhyperpolarization; circadian rhythm
Copyright © 2003 Society for Neuroscience 0270-6474/03/2351593-12$05.00/0
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