Afterhyperpolarization Regulates Firing Rate in Neurons of the Suprachiasmatic Nucleus

• Published in: The Journal of neuroscience Vol. 23; no. 5; pp. 1593 - 1604
• Main Authors: Cloues, Robin K, Sather, William A
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.03.2003; Society for Neuroscience
• Subjects: 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
• ISSN: 0270-6474; 1529-2401; 1529-2401
• 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.