Purpose: To determine the molecular and functional expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in developing and mature dopaminergic amacrine cells (DACs), the sole source of ocular dopamine that plays a vital role in visual function and eye development.
Methods: HCN channels are encoded by isoforms 1-4. HCN1, HCN2, and HCN4 were immunostained in retinal slices obtained from mice at postnatal day 4 (P4), P8, and P12 as well as in adults. Each HCN channel isoform was also immunostained with tyrosine hydroxylase, a marker for DACs, at P12 and adult retinas. Genetically-marked DACs were recorded in flat-mount retina preparation using a whole-cell current-clamp technique.
Results: HCN1 was expressed in rods/cones, amacrine cells, and retinal ganglion cells (RGCs) at P4, along with bipolar cells by P12. Different from HCN1, HCN2 and HCN4 were each expressed in amacrine cells and RGCs at P4, along with bipolar cells by P8, and in rods/cones by P12. Double immunostaining shows that each of the three isoforms was expressed in approximately half of DACs at P12 but in almost all DACs in adults. Electrophysiology results demonstrate that HCN channel isoforms form functional HCN channels, and the pharmacological blockade of HCN channels reduced the spontaneous firing frequency in most DACs.
Conclusions: Each class of retinal neurons may use different isoforms of HCN channels to function during development. HCN1, HCN2, and HCN4 form functional HCN channels in DACs, which appears to modulate their spontaneous firing activity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291019 | PMC |
| http://dx.doi.org/10.1101/2024.07.20.604440 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Combination of Autodisplay and Dynamic Pharmacophore Modeling Reveals New Insights into Cyclic Nucleotide Binding in Hyperpolarization-Activated and Cyclic Nucleotide-Gated Ion Channel 4 (HCN4).
ACS Pharmacol Transl Sci
December 2024
University of Münster, Institute of Pharmaceutical and Medicinal Chemistry, Pharma Campus, Corrensstr. 48, 48149 Münster, Germany.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels play a critical role in regulating neuronal and cardiac rhythmicity, with their function being modulated by cyclic nucleotide binding. Dysfunction of HCN ion channels leads to the genesis of several diseases such as arrhythmia, bradycardia, or epilepsy. This study employs a multidisciplinary approach integrating mutagenesis, ligand binding assays, and molecular dynamics (MD) simulations combined with dynamic pharmacophore studies to investigate the impact of single residue mutations within the cyclic nucleotide-binding domain (CNBD) of HCN4 channels.
View Article and Find Full Text PDFSpinal Nerve Axotomy: Effects on I In Vivo and HCNs in DRG Neurons.
Int J Mol Sci
November 2024
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan,430030, China.
In vitro experiments performed on dissociated dorsal root ganglion (DRG) neurons suggest the involvement of the hyperpolarization-activated cation current (I) in enhancing neuronal excitability, potentially contributing to neuropathic pain. However, the more confirmative in vivo information about how nerve injury interacts with I is lacking. In this study, I was recorded in vivo using the dynamic single-electrode voltage clamp (dSEVC) technique on L5 DRG neurons of normal rats and those seven days after spinal nerve axotomy (SNA).
View Article and Find Full Text PDFDeciphering the peculiarities of cell types in the septum.
Neuroscience
November 2024
Center for Biomedical Studies, Department of Biological Sciences, University of Texas at Brownsville, TX 78520, USA; Laboratory of Emotions' Neurobiology, Instytut Biologii Doświadczalnej im. M. Nenckiego PAN, Poland; Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon 1649, Portugal; Institute of Biophysics, Johannes Kepler University, Linz, Austria. Electronic address:
Similar to other brain regions, the neurons in the lateral septum (LS) are of heterogeneous populations. However, their resting membrane potential (RMP) on average is not too far apart. Cells were characterized based on biological markers by using brain slices, as under these in vitro conditions, neurons retain their morphologies.
View Article and Find Full Text PDFInterleukin-6 Modulates the Expression and Function of HCN Channels: A Link Between Inflammation and Atrial Electrogenesis.
Int J Mol Sci
November 2024
Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy.
Inflammatory cytokines, including interleukin 6 (IL6), are associated with ion channel remodeling and enhance the propensity to alterations in cardiac rhythm generation and propagation, in which the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a crucial role. Hence, we investigated the consequences of exposure to IL6 on HCN channels in cell models and human atrial biopsies. In murine atrial HL1 cells and in cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs), IL6 elicited STAT3 phosphorylation, a receptor-mediated downstream signaling.
View Article and Find Full Text PDFGlucocorticoids Selectively Inhibit Hippocampal CA1 Pyramidal Neurons Activity Through HCN Channels.
Int J Mol Sci
November 2024
Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai 200438, China.
Glucocorticoids are known to influence hippocampal function, but their rapid non-genomic effects on specific neurons in the hippocampal trisynaptic circuit remain underexplored. This study investigated the immediate effects of glucocorticoids on CA1 and CA3 pyramidal neurons, and dentate gyrus (DG) granule neurons in rats using the patch-clamp technique. We found that a 5 min extracellular application of corticosterone significantly reduced action potential firing frequency in CA1 pyramidal neurons, while no effects were observed in CA3 or DG neurons.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!