Circadian Regulation of A-Type Potassium Currents in the Suprachiasmatic Nucleus
- 1 February 2010
- journal article
- research article
- Published by American Physiological Society in Journal of Neurophysiology
- Vol. 103 (2), 632-640
- https://doi.org/10.1152/jn.00670.2009
Abstract
In mammals, the precise circadian timing of many biological processes depends on the generation of oscillations in neural activity of pacemaker cells in the suprachiasmatic nucleus (SCN) of the hypothalamus. Understanding the ionic mechanisms underlying these rhythms is an important goal of research in chronobiology. Previous work has shown that SCN neurons express A-type potassium currents (IAs), but little is known about the properties of this current in the SCN. We sought to characterize some of these properties, including the identities of IA channel subunits found in the SCN and the circadian regulation of IA itself. In this study, we were able to detect significant hybridization for Shal-related family members 1 and 2 (Kv4.1 and 4.2) within the SCN. In addition, we used Western blot to show that the Kv4.1 and 4.2 proteins are expressed in SCN tissue. We further show that the magnitude of the IA current exhibits a diurnal rhythm that peaks during the day in the dorsal region of the mouse SCN. This rhythm seems to be driven by a subset of SCN neurons with a larger peak current and a longer decay constant. Importantly, this rhythm in neurons in the dorsal SCN continues in constant darkness, providing an important demonstration of the circadian regulation of an intrinsic voltage-gated current in mammalian cells. We conclude that the anatomical expression, biophysical properties, and pharmacological profiles measured are all consistent with the SCN IA current being generated by Kv4 channels. Additionally, these data suggest a role for IA in the regulation of spontaneous action potential firing during the transitions between day/night and in the integration of synaptic inputs to SCN neurons throughout the daily cycle.Keywords
This publication has 56 references indexed in Scilit:
- Circadian regulation of ion channels and their functionsJournal of Neurochemistry, 2009
- Expression of the Circadian Clock Gene Period2 in the Hippocampus: Possible Implications for Synaptic Plasticity and Learned BehaviourASN Neuro, 2009
- Weighing the evidence for a ternary protein complex mediating A‐type K+ currents in neuronsThe Journal of Physiology, 2008
- Tetraethylammonium (TEA) increases the inactivation time constant of the transient K+ current in suprachiasmatic nucleus neuronsBrain Research, 2008
- Select cognitive deficits in Vasoactive Intestinal Peptide deficient miceBMC Neuroscience, 2008
- Excitatory Actions of GABA in the Suprachiasmatic NucleusJournal of Neuroscience, 2008
- Regulation of Dendritic Excitability by Activity-Dependent Trafficking of the A-Type K+ Channel Subunit Kv4.2 in Hippocampal NeuronsNeuron, 2007
- Molecular components of the mammalian circadian clockHuman Molecular Genetics, 2006
- Brain-derived neurotrophic factor and neurotrophin receptors modulate glutamate-induced phase shifts of the suprachiasmatic nucleusEuropean Journal of Neuroscience, 2006
- Coordination of circadian timing in mammalsNature, 2002