Carboplatin resistance in retinoblastoma, an aggressive pediatric intraocular tumor, remains a major clinical challenge in treatment. This study elucidates the role of T-type calcium channels in carboplatin resistance using human retinoblastoma Y79 cells. We generated carboplatin-resistant Y79 (Y79CR) cells and characterized their electrophysiological properties. Patch-clamp recordings revealed a subpopulation of enlarged Y79CR cells (i.e., giant cells) with hyperpolarized resting membrane potentials, reduced input resistance, and increased T-type calcium currents. Quantitative RT-PCR analysis confirmed upregulation of Ca3.3 mRNA in Y79CR cells, identifying Ca3.3 as the predominant channel mediating these currents. Pharmacological inhibition of Ca3.3 using ML218 and TAT-C3P attenuated the sustained currents and partially restored carboplatin sensitivity, as evidenced by decreased IC values in Y79CR cells. These findings demonstrate a critical role for T-type calcium channels, particularly Ca3.3, in mediating chemoresistance in retinoblastoma. Our results suggest that targeting these channels may provide a potential strategy to enhance the efficacy of carboplatin-based therapy in retinoblastoma treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850143 | PMC |
| http://dx.doi.org/10.1016/j.jbc.2025.108199 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CACNA1G, A Heterotaxy Candidate Gene, Plays a Role in Ciliogenesis and Left-Right Patterning in Xenopus tropicalis.
Genesis
February 2025
Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Heterotaxy (HTX) is characterized by an abnormality in the organ arrangement along the Left-Right (LR) axis and is caused by the disruption of LR patterning in early development. LR asymmetry is critical for multiple organs. Specifically, proper LR patterning is crucial for cardiac function and is a cause of congenital heart disease (CHD).
View Article and Find Full Text PDFCassan Diterpenoids with Cav3.1 T-type Calcium Channel Inhibitory Activity from the Seeds of Caesalpinia decapetala (Roth) Alston.
Chem Biodivers
February 2025
Yunnan Minzu University, Key laboratory of ethnic medicine resource chemistry, state ehnic affairs commission & Ministry of education, 2929# yuehua street, 650504, Kunming, CHINA.
Phytochemical investigation of the 80% ethanol extract from the seeds of Caesalpinia decapetala (Roth) Alston led to the identification of nine compounds, which included three new cassane-type diterpenoids, caesalpideplins A-C (1-3), and six known analogues (4-9). The structures of 1-3 were determined using a comprehensive analytical method that involved detailed IR, HRESIMS, 1H, 13C, and 2D NMR analyses. The absolute configuration of 1 was established through X-ray single crystal diffraction analysis, while the absolute configurations of 2 and 3 were determined by comparing their calculated and experimental ECD data.
View Article and Find Full Text PDFMuscarinic receptor activation preferentially inhibits rebound in vulnerable dopaminergic neurons.
J Neurosci
February 2025
Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007
Dopaminergic subpopulations of the substantia nigra (SNc) differentially degenerate in Parkinson's disease and are characterized by unique electrophysiological properties. The vulnerable population expresses a T-type calcium channel-mediated afterdepolarization (ADP) and shows rebound activity upon release from inhibition, whereas the resilient population does not have an ADP and is slower to fire after hyperpolarization. This rebound activity can trigger dopamine release in the striatum, an important component of basal ganglia function.
View Article and Find Full Text PDFEAD Mechanisms in Hypertrophic Mouse Ventricular Myocytes: Insights from a Compartmentalized Mathematical Model.
Bull Math Biol
February 2025
Department of Mathematics and Statistics, Georgia State University, 25 Park Place, Room 1346, Atlanta, GA, 30303-3083, USA.
Transverse aortic constriction (TAC) is one of the experimental mouse models that are designed to investigate cardiac hypertrophy and heart failure. Most of the studies with this model are devoted to the stage of developed heart failure. However, several studies of the early stages (hypertrophy after 1 week of TAC) of this disease found significant changes in the β-adrenergic system, electrical activity, and Ca dynamics in mouse ventricular myocytes.
View Article and Find Full Text PDFT-type calcium channels regulate medulloblastoma and can be targeted for therapy.
J Neurooncol
February 2025
Department of Microbiology, Immunology & Cancer Biology, University of Virginia, Charlottesville, VA, 22908, USA.
Purpose: The goal of this study was to investigate the role and therapeutic targeting of T-type calcium channels in medulloblastoma, a common and deadly pediatric brain tumor that arises in the cerebellum.
Methods: T-type calcium channel expression was assessed in publicly available bulk and single cell RNA-seq datasets. The effects of T-type calcium channel blocker mibefradil on cell growth, death and invasion were assessed with cell counting, alamar blue, trypan blue and transwell assays.
Want 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!