Voltage-activated Ca(2+) channels comprise complexes of a pore-forming Ca(V)alpha(1) and auxiliary subunits Ca(V)beta, Ca(V)alpha(2)delta and sometimes Ca(V)gamma. The intracellular Ca(V)beta subunit assists in trafficking and surface expression of the Ca(V)alpha(1) subunit and can modulate biophysical properties of the Ca(2+) channel. Four genes, Ca(V)beta1-4, exist which confer different properties to Ca(2+) currents through the various Ca(V)alpha(1) subunits. Ca(2+) currents in cochlear inner (IHC) and outer hair cells (OHC) serving synaptic transmission flow predominantly through the L-type Ca(V)alpha(1) subunit Ca(V)1.3, but associated Ca(V)beta subunits are unknown. In the organ of Corti, we found mRNA and protein for all four Ca(V)beta subunits including Ca(V)beta2, but clear assignment of the Ca(V)beta1-4 immunolabelling with hair cells or nerve fibers was difficult. We analyzed Ca(V)beta3 knockout (Ca(V)beta3(-/-)) and Ca(V)beta4 mutant mice (Ca(V)beta4(lh/lh)), which had normal hearing. Recording voltage-activated Ba(2+) currents from hair cells of the two mouse models revealed distinct significant changes of cell size and Ba(2+) current properties compared with their wild-type controls. Neonatal Ca(V)beta4(lh/lh) IHCs showed reduced membrane capacitances and changes in the voltage dependence and kinetics of current activation, whereas mature IHCs had reduced peak currents compared with Ca(V)beta4(wt), altogether indicating the presence of Ca(V)beta4 in IHCs. Ba(2+) currents of Ca(V)beta3(-/-) OHCs showed largely reduced amplitudes, changes in the voltage dependence and kinetics of Ba(2+) current activation, and increased inactivation compared with Ca(V)beta3(wt), pointing to a role of Ca(V)beta3 for OHCs. These results indicate that neither Ca(V)beta3 nor Ca(V)beta4 are indispensable for hair cell Ca(2+) currents but contribute to the overall current properties.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4161/chan.3.5.9774 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The empowering influence of air-liquid interface culture on skin organoid hair follicle development.
Burns Trauma
January 2025
Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4102Australia.
Background: Rodent models have been widely used to investigate skin development, but do not account for significant differences in composition compared to human skin. On the other hand, two-dimensional and three-dimensional engineered skin models still lack the complex features of human skin such as appendages and pigmentation. Recently, hair follicle containing skin organoids (SKOs) with a stratified epidermis, and dermis layer have been generated as floating spheres from human-induced pluripotent stem cells (hiPSCs).
View Article and Find Full Text PDFEmbryonic Mammary Gland Morphogenesis.
Adv Exp Med Biol
January 2025
Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Helsinki, Finland.
Embryonic mammary gland development unfolds with the specification of bilateral mammary lines, thereafter progressing through placode, bud, and sprout stages before branching morphogenesis. Extensive epithelial-mesenchymal interactions guide morphogenesis from embryogenesis to adulthood. Two distinct mesenchymal tissues are involved, the primary mammary mesenchyme that harbors mammary inductive capacity, and the secondary mesenchyme, the precursor of the adult stroma.
View Article and Find Full Text PDFInflammasome activation in melanoma progression: the latest update concerning pathological role and therapeutic value.
Arch Dermatol Res
January 2025
Uttaranchal Institute of Pharmaceutical Sciences, Division of research and innovation, Uttaranchal University, Dehradun, Uttarakhand, India.
The progression of melanoma is a complex process influenced by both internal and external cues which encourage the transition of tumour cells, uncontrolled growth, migration, and metastasis. Additionally, inflammation allows tumours to evade the immune system, contributing to cancer development. The inflammasome, a complex of many proteins, is crucial in enhancing immune responses to external and internal triggers.
View Article and Find Full Text PDFInnovative treatment of age-related hearing loss using MSCs and EVs with Apelin.
Cell Biol Toxicol
January 2025
Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Utilizing single-cell transcriptome sequencing (scRNA-seq) technology, this study explores the viability of employing mesenchymal stem cells (MSCs) as a therapeutic approach for age-related hearing loss (ARHL). The research demonstrates MSCs' ability to differentiate into inner ear cell subpopulations, particularly hair cells, delivering Apelin via extracellular vesicles (EVs) to promote M2 macrophage polarization. In vitro experiments show reduced inflammation and preservation of hair cell health.
View Article and Find Full Text PDFNanoparticle Adjuvants Incorporating Haptens Drive Potent Immune Tolerance to Accelerate Hair Regrowth.
ACS Appl Mater Interfaces
January 2025
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Alopecia areata (AA) is a prevalent autoimmune condition that causes sudden hair loss and poses significant psychological challenges to affected individuals. Current treatments, including corticosteroids and Janus kinase inhibitors, fail to provide long-term efficacy due to adverse effects and relapse after cessation. This study introduces a nanoparticle (NP) system that codeliver diphenylcyclopropenone (DPCP) and rapamycin (RAPA) prodrugs to induce immune tolerance and promote hair regeneration.
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!