Pathology and physiology of acid-sensitive ion channels in the bladder

Acid-sensitive ion channels (ASICs) are sodium-permeable channels activated by extracellular acidification. They can be activated and trigger the inward flow of Na⁺ when the extracellular environment is acidic, leading to membrane depolarization and thus inducing action potentials in neurons. There are four ASIC genes in mammals (ASIC1-4). ASIC is widely expressed in humans. It is closely associated with pain, neurological disorders, multiple sclerosis, epilepsy, migraines, and many other disorders. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a specific syndrome characterized by bladder pain. Recent studies have shown that ASICs are closely associated with the development of BPS/IC. A study revealed that ASIC levels are significantly elevated in a BPS/IC model. Additionally, researchers have reported differential changes in ASICs in the bladders of patients with neurogenic lower urinary tract dysfunction (NLUTD) caused by spinal cord injury (SCI). In this review, we summarize the structure and physiological functions of ASICs and focus on the mechanisms by which ASICs mediate bladder disease.