Legacy Ion-Channel Drugs as Controllers of Tissue Bioelectric Goal States

Bioelectric signaling regulates development, regeneration, and cancer suppression. This computational study introduces a minimal control-logic framework bridging ion channel pharmacology to multicell bioelectric patterning in regeneration (e.g., Xenopus limbs, planarian polarity). Using dimensionless ordinary differential equations anchored to pharmacological timescales (e.g., propranolol PK, hours), we modeled three ion channel drugs (amiloride, propranolol, ivermectin) in single cells, embedded them in gap-junction-coupled 10 × 10 tissue lattices, and applied DEAP evolutionary optimization to recover target Vmem patterns. Multiple (k ₁ , k ₂ , k ₃ ) parameter sets yielded identical tissue-scale Vmem patterns, despite perturbations such as ivermectin-induced 2 × k ₃ Cl⁻ scaling. This parameter robustness positions tissues as active controllers maintaining patterning goals amid variability. Simulated legacy drugs controlled tissue-level bioelectric/voltage goal states, and different microscopic configurations were able to reach a target voltage state following in silico evolutionary optimization of a few parameters. New predictions include depolarizing Na ⁺ blockade inducing ectopic posteriorization and hyperpolarizing Cl⁻ activation restoring anterior–posterior Vmem gradients in planarian regeneration. This is falsifiable with CC2-DMPE dyes. These simulations could reframe legacy ion-channel drugs as bioelectric goal-state controllers beyond single-target inhibition, providing an extensible quantitative systems pharmacology pipeline (GitHub: Cameron-99/bioelectric-qsp-model) for multi-physics models and bioelectricity research.