Integrative Pharmacology of Calcium and Ion Channels: Unraveling Disease Mechanisms through Genetic, Epigenetic, and Post-Translational Modifications

Ion channels are not static molecular machines. Their functional states — and by extension, their pharmacological profiles — are continuously shaped by the cellular environment through genetic variation, epigenetic reprogramming, and post-translational modification (PTM). Yet much of the channelopathy literature still treats channel dysfunction as a binary problem: a mutation is present, a current is aberrant, a drug blocks it. This Research Topic challenges that reductionist framing.The pharmacological behavior of calcium and other ion channels cannot be fully understood in isolation from the regulatory layers that govern their expression, trafficking, and gating. Phosphorylation, glycosylation, SUMOylation, and ubiquitination can each alter drug-binding kinetics, channel localization, and state-dependent gating in ways that profoundly affect therapeutic outcomes. Similarly, epigenetic silencing or upregulation of channel subunits — and the microRNAs that regulate them — can remodel the electrophysiological landscape of a cell in disease states ranging from cardiac arrhythmia to neuropathic pain to epilepsy. Genetic variants, whether rare Mendelian mutations or common polymorphisms with modest effect sizes, add a further layer of complexity that determines individual susceptibility and drug response.This Research Topic prioritizes work that integrates these regulatory dimensions into a coherent pharmacological framework. We are specifically interested in studies that move beyond channel characterization toward a mechanistic understanding of how modification state determines drug sensitivity, resistance, or off-target effects.We invite original research, reviews, and perspectives that address:Genetic Architecture of Channelopathies: Studies examining how pathogenic variants — including gain- and loss-of-function mutations — alter channel pharmacology, gating kinetics, or drug binding. Particular interest in variants with translational relevance to precision therapeutics.Epigenetic Regulation of Channel Expression: Investigations into how DNA methylation, histone modification, or non-coding RNAs modulate the expression of ion channel subunits in disease contexts, and how these changes affect pharmacological intervention.Post-Translational Modification and Drug Response: Mechanistic studies linking specific PTMs (phosphorylation, glycosylation, ubiquitination, SUMOylation, palmitoylation) to altered channel function, pharmacokinetics at the channel level, or therapeutic sensitivity.Calcium Signaling Dysregulation: Research addressing how disrupted Ca²⁺ homeostasis — arising from channelopathy, PTM crosstalk, or epigenetic remodeling — contributes to pathophysiology in cardiac, neurological, or musculoskeletal disease.Integrative and Multi-Omic Approaches: Work that combines transcriptomic, proteomic, or epigenomic datasets with functional electrophysiology to generate pharmacologically actionable insights.Translational Pharmacology: Studies bridging mechanistic findings to therapeutic strategies, including novel channel modulators, gene therapy approaches, or biomarker development for patient stratification.This Research Topic sits at the intersection of molecular pharmacology, electrophysiology, and systems biology. We welcome contributions from researchers working across disease areas — including cardiac arrhythmia, epilepsy, chronic pain, and skeletal muscle disorders — provided that the pharmacological and mechanistic dimensions are explicitly addressed. Topic editors: Dana-Lynn Koomoa-Lange, Santiago Partida Sanchez, Ingo Lange Source: https://www.frontiersin.org/research-topics/81508/integrative-pharmacology-of-calcium-and-ion-channels-unraveling-disease-mechanisms-through-genetic-epigenetic-and-post-translational-modifications