Restoring Bioelectric Timing Fidelity to Prevent Immune Dysregulation

Non‑thermal biological effects of low‑frequency/pulsed radio‑frequency fields (LF/RF‑EMFs) can be parsimoniously explained by a timing‑fidelity mechanism anchored in ion‑channel biophysics. Voltage‑gated ion channels (VGICs) detect transmembrane potential via the S4 voltage sensor; a local potential change ΔV across the ~1 nm sensing region shifts the activation free energy by ΔG = zₑff e ΔV, altering opening/closing rate constants. With a representative zₑff ≈ 3 e₀, a ΔV = 30 mV perturbation changes ΔG by ~0.09 eV (~3.5 kBT), producing >30‑fold changes in opening rates. Such deterministic shifts advance or delay gating in Kv1.3/KCa3.1, Nav/Cav/HCN, and ORAI1–STIM1 (CRAC), thereby re‑specifying K⁺, Ca²⁺, and H⁺ flux independent of tissue heating.

In lymphocytes, Kv1.3/KCa3.1 set the hyperpolarization that sustains CRAC influx; ORAI1–STIM1 then imposes Ca²⁺ spike timing that drives NFAT/NF‑κB transcription. In phagocytes, HVCN1 provides charge/pH compensation for the NADPH‑oxidase respiratory burst. Millivolt‑scale shifts in these gating steps alter Ca²⁺ waveforms and oxidase matching, producing inappropriate cytokine programs and oxidative signaling. The resulting mitochondrial workload/Ca²⁺ imbalance elevates mtROS and releases mtDNA, activating cGAS–STING, TLR9, and NLRP3, which feed back to channel expression and redox‑sensitive residues—stabilizing chronic inflammation and erosion of tolerance. Tissues with high VGIC and mitochondrial density (heart, nerve) are predicted to be most susceptible, consistent with animal carcinogenicity signals (malignant cardiac schwannomas; gliomas) and sensitive reproductive/pregnancy endpoints reported in recent literature.

We outline falsifiable tests: (i) V½/slope and open‑time distribution shifts in VGICs under equal‑power but differently pulsed exposures; (ii) quantitative changes in Ca²⁺ spike intervals and NFAT nuclear‑entry timing; (iii) HVCN1–oxidase coupling curves; (iv) mtROS, Δψm, cf‑mtDNA, and cGAS–STING/TLR9/NLRP3 activation with pharmacologic rescue. Finally, we propose an engineering/health policy program—Clean Ether Act—that reduces controllable indoor RF burdens, emphasizes temporal patterning (duty cycle, peak‑to‑average) in device performance standards, and shifts high‑capacity links to LiFi (IEEE 802.11bb) with IEC 62471‑7 photobiological safety, prioritizing protections for children and pregnancy.