Biology subjects

Naveed, M.

Publications and source records attributed to Naveed, M..

3 recordsLinked to original sources

bioRxiv2026

Multi-scale electrophysiological characterization of human cardioids reveals progressive maturation

Background: Human induced pluripotent stem cell-derived cardiomyocytes are valuable for cardiac disease modelling and drug testing but remain limited by immature structural and electrophysiological properties in conventional two-dimensional cultures. Three-dimensional cardiac models, including cardioids, provide a more physiological environment through multicellular organization and enable tissue-level functional analysis. Their electrophysiological properties and maturation, however, remain incompletely characterized. Methods: We performed an integrated electrophysiological characterization of human cardioids over the first three weeks of maturation using sharp microelectrode recordings, calcium transient measurements, whole-cell patch clamp recordings, immunofluorescence, transcriptomic analysis, and pharmacological interventions. Results: During maturation, cardioids exhibited progressive electrophysiological maturation, characterized by more physiological resting membrane potentials (-54.0{+/-}3.1mV to -68.1{+/-}1.2mV), increased action potential amplitude (73.5{+/-}4.8mV to 101.7{+/-}2.1mV) and upstroke velocity (44.3{+/-}5mV/ms to 86.6{+/-}8.4mV/ms), and shorter action potential duration (178.9{+/-}8.7ms to 144.0{+/-}4.8ms at 1Hz stimulation). These changes were associated with progressively increased INa density and enhanced SCN5A mRNA and Nav1.5 protein expression, consistent with progressive maturation of cardiac excitability. IKr current and KCNH2/hERG expression were already present at early maturation stages and remained stable, as evidenced by preserved sensitivity to dofetilide-blockade. Pharmacological inhibition of barium- and HMR-sensitive currents altered resting membrane and/or action potential characteristics in intact cardioids, whereas in isolated cardiomyocytes classical IK1 remained undetectable and IKs was small, highlighting a certain degree of persisting immaturity of the model. Conclusions: These findings demonstrate that human cardioids undergo progressive electrophysiological maturation and provide complementary tissue- and cellular-level insights into cardiac function, establishing their suitability for investigating INa and IKr-related cardiac pathologies.

physiology↗

bioRxiv2023

Lights, Camera, Mirrors, Action! Toolbox for 3D Reconstruction and Analysis Using a Single Camera and Planar Mirrors

The advent of high-speed cameras being made available for commercial use has facilitated the discovery of intriguing animal behaviors. However, analyzing animal kinematics in three dimensions necessitates using several high-speed cameras, which are specialized equipment and come at a significant expense. In this study, we utilize a conventional methodology of capturing synchronized multiple views using a solitary camera and planar mirrors. We introduce a user-friendly software package that facilitates the calibration of this economical setup and enables the three-dimensional (3D) analysis of high-rate maneuvers. Within[~] 15 minutes, a single high-speed camera is calibrated and can be used to acquire 3D data. We accompany the toolbox with a detailed user guide and video tutorial (https://tinyurl.com/yckm9y6b) for ease of use. We accurately reconstruct the wing beats of multiple flies (dragonfly, butterfly).

animal behavior and cognition↗

bioRxiv2022

Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise

The health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. While some studies after endurance training have been performed in small animals these have limited translation value. Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (QTc: 213.6{+/-}2.8 ms vs. 237.1{+/-}3.4 ms, n=12; APD90: 370.1{+/-}32.7 ms vs. 472.8{+/-}29.6 ms, n=25 vs. 29), decreased transient outward potassium current (8.8{+/-}0.9 pA/pF vs. 6.4{+/-}0.5 pA/pF at 50 mV, n=42 vs. 54) and increased the short term variability of repolarization (17.5{+/-}4.0 ms vs. 29.5{+/-}3.8 ms, n=18 vs. 27). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of extrasystoles: 4/hour vs. 366/hour) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs). Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training.

physiology↗