biostudies-literatureUnknown11(1)Mohammadiaria MEnvironmental stressors such as radiation, pH shifts, temperature variations, and electromagnetic fields can trigger intracellular oxidative stress, upregulating voltage-gated ion channel (VGIC) gene expression. This paper presents a hybrid modeling framework integrating Hodgkin-Huxley-based electrophysiological simulations with redox-sensitive transcriptional feedback to investigate how reactive oxygen species (ROS) modulate calcium signaling and drive electrophysiological reprogramming. In healthy epithelial cells (MCF-10A), sustained oxidative perturbations induce non-voltage-gated calcium influx, mitochondrial ROS generation, and VGIC transcription, shifting membrane potential from non-excitable to excitable states. Repeated ROS or thermal pulses promote progressive VGIC expression, deNPJ systems biology and applications119https://www.ebi.ac.uk/biostudies/studies/S-EPMC12559232biostudies-literatureROS-induced voltage-gated ion channel expression and electrophysiological remodeling in malignant human cells.PMC12559232Mohammadiaria MfalseROS-induced voltage-gated ion channel expression and electrophysiological remodeling in malignant human cells.Environmental stressors such as radiation, pH shifts, temperature variations, and electromagnetic fields can trigger intracellular oxidative stress, upregulating voltage-gated ion channel (VGIC) gene expression. This paper presents a hybrid modeling framework integrating Hodgkin-Huxley-based electrophysiological simulations with redox-sensitive transcriptional feedback to investigate how reactive oxygen species (ROS) modulate calcium signaling and drive electrophysiological reprogramming. In healthy epithelial cells (MCF-10A), sustained oxidative perturbations induce non-voltage-gated calcium influx, mitochondrial ROS generation, and VGIC transcription, shifting membrane potential from non-excitable to excitable states. Repeated ROS or thermal pulses promote progressive VGIC expression, de2025-01-01T00:00:00Z2025 Oct2026-07-15T11:59:25.207Z2026-07-04T03:12:40.63ZS-EPMC125592324114550910.1038/s41540-025-00595-x