Ion Channels as Therapeutic Targets in Overactive Bladder: A Narrative Review of Mechanisms, Translational Evidence, and Current Gaps.

Overactive bladder (OAB) is a prevalent syndrome whose first-line pharmacotherapy with antimuscarinics and β3-adrenoceptor agonists is limited by suboptimal efficacy and poor tolerability, underscoring the unmet need for novel molecular targets. As key regulators of detrusor smooth muscle excitability and bladder afferent signaling, ion channels have emerged as a compelling target class capable of modulating bladder function with high spatial precision. This review summarizes current evidence on the role of cation and anion channels in OAB pathophysiology and critically appraises their therapeutic potential, covering the principal channel families implicated in detrusor and afferent dysfunction, including voltage-gated Ca2+ and Na+ channels, K+ channel subfamilies, HCN, TRP, and PIEZO channels, ligand-gated cation channels, ENaC/ASIC, and Cl- channels, with preclinical and clinical evidence integrated throughout. Despite this strong mechanistic rationale, clinical translation has been hampered by ubiquitous channel expression, patient heterogeneity, and the absence of stratifying biomarkers. Although the supporting evidence remains uneven, spanning genetic, ex vivo, and early-phase clinical studies, future progress will likely depend on tissue-selective compounds, biomarker-defined subphenotypes, and emerging targets such as TMEM16A, TRPM4, and PIEZO channels, which represent particularly promising avenues for next-generation OAB pharmacotherapy.