The Mystery of the Interstitial Cells in the Urinary Bladder

Intrinsic mechanisms to restrain smooth muscle excitability are present in the bladder, and premature contractions during filling indicate a pathological phenotype. Some investigators have proposed that c-Kit⁺ interstitial cells (ICs) are pacemakers and intermediaries in efferent and afferent neural activity, but recent findings suggest these cells have been misidentified and their functions have been misinterpreted. Cells reported to be c-Kit⁺ cells colabel with vimentin antibodies, but vimentin is not a specific marker for c-Kit⁺ cells. A recent report shows that c-Kit⁺ cells in several species coexpress mast cell tryptase, suggesting that they are likely to be mast cells. In fact, most bladder ICs labeled with vimentin antibodies coexpress platelet-derived growth factor receptor α (PDGFRα). Rather than an excitatory phenotype, PDGFRα⁺ cells convey inhibitory regulation in the detrusor, and inhibitory mechanisms are activated by purines and stretch. PDGFRα⁺ cells restrain premature development of contractions during bladder filling, and overactive behavior develops when the inhibitory pathways in these cells are blocked. PDGFRα⁺ cells are also a prominent cell type in the submucosa and lamina propria, but little is known about their function in these locations. Effective pharmacological manipulation of bladder ICs depends on proper identification and further study of the pathways in these cells that affect bladder functions.