Interstitial cell of Cajal-like cells in the upper urinary tract

Abstract

Autorhythmicity in the upper urinary tract (UUT) has long been considered to arise in specialized atypical smooth muscle cells (SMC) predominately situated in the most proximal regions of the pyeloureteric system. These atypical SMC pacemakers have been thought to trigger adjacent electrically-quiescent typical SMC to fire action potentials which allow an influx of Ca 2+ and the generation of muscle contraction. More recently, the presence of cells with many of the morphological, electrical and immunohistochemical characteristics of interstitial cells of Cajal (ICC), the pacemaker cells of the gastrointestinal tract, have been located in many regions of both the upper and lower urinary tract. This article reviews the evidence from the literature and from our laboratory supporting a role of both atypical SMC and ICC-like cells in the initiation and propagation of pyeloureteric peristalsis in the UUT. We propose a new model in which there are 2 populations of pacemaker cells, high frequency atypical SMC and lower frequency ICC-like cells, both of which can drive electrically-quiescent typical SMC. The relative presence of these 2 populations of pacemaker cells and the relatively-long refractoriness of typical SMC determines the decreasing frequency of contraction with distance from the renal fornix. In the absence of the proximal pacemaker drive from atypical SMC after pyeloureteral/ureteral obstruction or surgery, ICC-like cell pacemaking provides a compensatory mechanism allowing the ureter to maintain rudimentary peristaltic waves and movement of urine from the pyelon towards the bladder.

Cajal-type cells from human mammary gland stroma: phenotype characteristics in cell culture

“…However, after the year 2000, ICC-like cells (ICC-LC) have been found outside the gastrointestinal tract (reviews in 2005: [3,4]). Our laboratory reported the identification (at actual and quasi-complete standards) of ICC-LC in human pancreas [5,6], uterus [7] and fallopian tube [8].…”

The effect of extracorporeal shock wave lithotripsy on distribution of interstitialcells of Cajal in rabbit renal pelvis and proximal ureter

“…However, the exact mechanism of Table. The median values of the histopathological grades (interquartile ranges within parentheses). this propelling movement and the factors deteriorating it are not clear (6,13,14). This peristalsis occurs even after surgical denervation of ureter or isolation of the pyeloureteric system, indicating autonomous pacemaker activity (6,13,14).…”

“…They are found less frequently in pig, for example. On the other hand, differentiation of them requires species-specific antibodies (6,13,14). Therefore, further studies are needed to examine the longterm effects of ESWL on ureteric peristalsis.…”

“…Some spindle-shaped c-kit-positive cells were detected in the UUT. They were differentiated from other c-kit-positive cells, such as mast cells, by additional staining with mast cell markers, and were called Cajal-like cells (6,13,14). These cells are usually found within smooth muscle layers of the UUT.…”

“…This peristalsis occurs even after surgical denervation of ureter or isolation of the pyeloureteric system, indicating autonomous pacemaker activity (6,13,14). Some pacemaker potentials were able to be shown by electrophysiological studies in the renal pelvis in animal studies (6,14). After recognition of ICCs in the gut (15,16), several studies were performed to investigate the presence and distribution of pacemaker cells in the UUT.…”