Restoring Bioelectric Timing Fidelity to Prevent Immune Dysregulation

Non‑thermal biological effects of low‑frequency/pulsed RF exposures arise from a timing‑fidelity mechanism in which external fields shift the voltage‑dependent activation energy of ion channels. Voltage‑gated channels sense transmembrane potential with the S4 helix; a local potential change $\Delta V$ across the ~1 nm sensing region shifts the barrier by ΔG=zeffe ΔV\Delta G = z_{\mathrm{eff}} e\,\Delta VΔG=zeff​eΔV. With a representative zeff≈3 e0z_{\mathrm{eff}} \approx 3\,e_0zeff​≈3e0​, $\Delta V=30$ mV changes $\Delta G$ by ~0.09 eV (~3.4 kBT), yielding a ~30‑fold change in opening rates. These 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 without heating.

In lymphocytes, Kv1.3/KCa3.1 set the hyperpolarization that sustains CRAC influx; ORAI1–STIM1 imposes Ca²⁺ spike timing that controls NFAT/NF‑κB transcription. In phagocytes, HVCN1 provides charge/pH compensation for the NADPH‑oxidase respiratory burst. Millivolt‑scale shifts at these checkpoints alter Ca²⁺ waveforms and oxidase coupling, producing inappropriate cytokine programs and oxidative signaling. The resulting mitochondrial Ca²⁺/workload mismatch elevates mtROS and releases mtDNA, activating cGAS–STING, TLR9, and NLRP3 and feeding back to channel expression—stabilizing chronic inflammation and loss of tolerance. Tissues with high VGIC density and mitochondrial content (heart, nerve) are the highest‑susceptibility sites, consistent with animal carcinogenicity signals and sensitive reproductive/pregnancy endpoints.

We outline falsifiable tests: (i) V½/slope/open‑time shifts under equal‑power, differently pulsed exposures; (ii) quantitative changes in Ca²⁺ spike intervals and NFAT nuclear entry; (iii) HVCN1–oxidase coupling; (iv) mtROS, Δψm, cf‑mtDNA, and cGAS–STING/TLR9/NLRP3 activation with pharmacologic rescue. We also propose performance‑based controls on duty cycle and peak‑to‑average ratio, and LiFi (IEEE 802.11bb) to reduce indoor RF while maintaining connectivity.

Keywords: voltage‑gated ion channels; S4 voltage sensor; Kv1.3; KCa3.1; ORAI1–STIM1; HVCN1; mtROS; mtDNA; cGAS–STING; NLRP3; timing fidelity; duty cycle; peak‑to‑average ratio; LiFi/IEEE 802.11bb.