Potassium channel subtypes as molecular targets for overactive bladder and other urological disorders

Abstract

Potassium channels have re-emerged as attractive targets for overactive bladder and other urological diseases in recent years, in part due to an enhanced understanding of their molecular heterogeneity, tissue distribution, functional roles and regulation in physiological and pathological states. Cloning and heterologous expression analysis, coupled with the advancement of improved high-throughput screening techniques, have enabled expeditious identification of selective small-molecule openers and blockers for ATP-sensitive K⁺ channels, Ca²⁺-activated K⁺ channels and voltage-dependent K⁺ channel-KQT-like subfamily (KCNQ) members, and has paved the way in the assessment of efficacy and adverse effects in preclinical models. This review focuses on the rationale for molecular targeting of K⁺ channels, the current status of target validation, including preclinical proof-of-concept studies, and provides perspectives on the limitations and hurdles to be overcome in realising the potential of these targets for diverse urological indications such as overactive bladder, erectile dysfunction and prostate diseases.

• ATP-sensitive K+ channels (KATP)
• Ca2+-activated K+ channels (KCa)
• erectile dysfunction
• molecular targets
• overactive bladder
• potassium channel opener (KCO)
• prostate cancer
• voltage-dependent K+ channel-KQT-like subfamily (KCNQ) channels