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

Berkay Demirçi1, Gülsüm Helvacı1,2, Elif Nur Barut2

  • 1Department of Pharmacology, Graduate School of Health Sciences, Karadeniz Technical University, Trabzon, Türkiye.

Lower Urinary Tract Symptoms
|July 13, 2026
PubMed

Insights

Ion channels are promising targets for overactive bladder (OAB) treatment, offering precise modulation of bladder function. Future therapies may focus on tissue-selective compounds and novel targets like TMEM16A, TRPM4, and PIEZO channels.

Area of Science:

  • Urology
  • Pharmacology
  • Physiology

Background:

  • Overactive bladder (OAB) pharmacotherapy faces challenges with current antimuscarinic and β3-adrenoceptor agonist treatments due to limited efficacy and tolerability.
  • Ion channels are critical regulators of detrusor smooth muscle excitability and bladder afferent signaling, presenting a target class for precise bladder function modulation.

Purpose of the Study:

  • To review current evidence on the role of cation and anion channels in OAB pathophysiology.
  • To critically appraise the therapeutic potential of various ion channel families for OAB treatment.

Main Methods:

  • Comprehensive review of preclinical and clinical evidence.
  • Integration of genetic, ex vivo, and early-phase clinical study data.
  • Focus on ion channel families including voltage-gated Ca2+ and Na+ channels, K+ channels, HCN, TRP, PIEZO, ligand-gated cation channels, ENaC/ASIC, and Cl- channels.

Main Results:

  • Ion channels are implicated in detrusor and afferent dysfunction in OAB.
  • Clinical translation of ion channel-targeted therapies is hindered by non-specific expression, patient heterogeneity, and lack of biomarkers.
  • Emerging targets like TMEM16A, TRPM4, and PIEZO channels show promise.

Conclusions:

  • Ion channels represent a compelling target class for novel OAB pharmacotherapy.
  • Future progress requires tissue-selective compounds and biomarker-defined patient subphenotypes.
  • TMEM16A, TRPM4, and PIEZO channels are particularly promising for next-generation OAB treatments.
Keywords:
PIEZO channelsTRP channelsdetrusor overactivityion channelsoveractive bladder

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