title: Afterhyperpolarization regulates firing rate in neurons of the suprachiasmatic nucleus.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: Robin K
authors.initials: RK
authors.lastname: Cloues
authors.forename: William A
authors.initials: WA
authors.lastname: Sather
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001683:Biological Clocks / Q000502:physiology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018756:GABA Antagonists; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D002104:Cadmium; D001030:Apamin; C064719:iberiotoxin