Background: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels help control the rhythmic activation of pacemaker neurons during brain development. However, little is known about the timing and cell type specificity of the expression of HCN isoforms during development of the hippocampus.
Results: Here we examined the developmental expression of the brain-enriched HCN1, HCN2, and HCN4 isoforms of HCN channels in mouse hippocampus from embryonic to postnatal stages. All these isoforms were expressed abundantly in the hippocampus at embryonic day 14.5 and postnatal day 0. Each HCN channel isoform showed subfield-specific expression within the hippocampus from postnatal day 7, and only HCN4 was found in glial cells in the stratum lacunosum moleculare at this developmental stage. At postnatal days 21 and 56, all HCN isoforms were strongly expressed in the stratum lacunosum moleculare and the stratum pyramidale of the Cornu Ammonis (CA), as well as in the hilus of the dentate gyrus, but not in the subgranular zone. Furthermore, the immunolabeling for all these isoforms was colocalized with parvalbumin immunolabeling in interneurons of the CA field and in the dentate gyrus.
Conclusions: Our mapping data showing the temporal and spatial changes in the expression of HCN channels suggest that HCN1, HCN2, and HCN4 subunits may have distinct physiological roles in the developing hippocampus.
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http://dx.doi.org/10.1186/s13041-015-0103-4 | DOI Listing |
NPJ Parkinsons Dis
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Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20852, USA.
ΑBSTRACT: In Parkinson's disease (PD), Lewy pathology deposits in the cerebral cortex, but how the pathology disrupts cortical circuit integrity and function remains poorly understood. To begin to address this question, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. We reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern.
View Article and Find Full Text PDFCells
December 2024
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control.
View Article and Find Full Text PDFNeurosci Lett
January 2025
Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi Dori, Chuo-Ku, Niigata City, Niigata 951-8510, Japan. Electronic address:
Spinal cord injuries (SCIs) can lead to severe neuropathic pain and increased risk of myocardial infarction and heart failure; therefore, the use of analgesics against SCI-induced pain should be minimized because of their adverse effects on the cardiovascular system. Ivabradine, a blocker of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, is used as a bradycardic agent, but recent studies focused on it as an analgesic agent for peripheral neuropathic pain. However, the analgesic effects of ivabradine on central neuropathic pain, such as SCI-induced pain, have not been examined.
View Article and Find Full Text PDFIn the human heart, the binding of cyclic adenosine monophosphate (cAMP), a second messenger, to hyperpolarization and cyclic nucleotide-gated (HCN) regulates the automaticity of pacemaker cells. Recent single-molecule binding studies show that cAMP bound to each subunit of purified tetrameric HCN channels independently, in contrast to findings in cells. To explore the lipid membrane's role in cAMP regulation, we reconstituted purified human HCN channels in various lipid nanodiscs and resolved single molecule ligand-binding dynamics.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
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