| Background and Objective: The ureter is an autorhythmical hollow muscular organ that propels urine from kidney to bladder. The anatomy shows that the ureter displays spontaneous contraction at 7-8times/min whatever it is used by the blockers of nerve function. This function ensures the unidirectional of urine and its key for metabolism. This phenomenon point out that may be ureter has spontaneous activity like the cardiac muscle and there is an area as pacemaker. Some of the patient display anuresis if the pelvis or the calyx has been impaired by the surgery of kidney transplant. At that moment ureter would peristalsis at low rates even if had no excitability and it could cause obstruction, infection, uraemia. Most of patient would pull through if the kidney transplant attached the whole upper urinary tract. So doing research in the origination of ureter's peristalsis and modulation would expatiate the deceases of obstruction in upper urinary tract also the treatment.For the past 40 years, the autorhythmicity in the upper urinary tract has long been considered to arise in specialized atypical smooth muscle cells. All the research are around the smooth muscle cell including the ultra structure of smooth muscle cells, the receptor expression, the phenotype transformation of smooth muscle cells and the change of gap junction intercellular communication. Especially found the atypical smooth muscle cells characterize its configuration and electrophysiology like the sinus. The atypical SMC predominately situated in the most proximal regions of the pyeloureteric system is suggested to be the pacemaker. But after using simultaneous extracellular recording in sheep renal pelvis reveal that there is only one pacemaker region at any one time. These observations do not support the concept of summation of subthreshold pacemaker activity. So we couldn't support the atypical SMC as pacemaker. More recently, the presence of cells with characteristic of interstitial cells of Cajal, the pacemaker in the gastrointestinal tract, have been located in many smooth muscle organs; some have been proved as the original of spontaneous activity.What about the ureter? Dose it have this type of cell? In the past several years, we have done some research work about this task, by the Chinese National Nature Science Foundation(code:30670776), we also found the c-kit positive cells in the guinea-pig upper urinary tract. Solari had contrasted 19 patients of UPJ obstruction with normal children in density of ICC from upper urinary tract. The result showed that it was lower in the UPJ obstruction patient and c-kit positive cells in normal children were wildly distributed. These results prompt that ICC may be play an important role in ureter's contraction and modulation. David SG used antibody of c-kit to foster mice, its ureter showed low excitability. Above all we thought UPJ may be the pacemaker region and ICCs probable is the pacemaker.To finish this study, we plan to do some works as following: first, by investigation of the variance of smooth muscle excitability in different locations of upper urinary tract, to explore the possibility of pacemaker site ; second, at the base of the results of part one, by the method of immunofluorescence histochemistry, to explore the presence of ICC-like cells in guinea-pig upper urinary tract .At last find out the correlation between ICC-like cells and smooth muscle excitability,Materials and methods: Normal guinea-pig of 8～10 weeks without sexual, weighing from 400-450g were used. The smooth muscle strips in ureteropelvic junction, upper ureteral, middle ureteral, lower ureteral tissues were harvested from guinea-pigs prepared for record of myoelectric contraction. The upper ureteral is 0.5 cm from the UPJ, the lower ureteral is 0.5cm from bladder and the middle ureteral is the mean of above. Smooth muscle strips were dissected from the sites for tone determination. Immunofluorescent was used to investigate the presence and distribution of ICC-like cells. And then the correlation between ICC-like cells and smooth muscle excitability was investigated. None of c-kit antibody was used as negative for contrast of positive one.Results:1. The contraction frequency and amplitude of the strips harvested from different locations of smooth muscle is different. Under the preload , the contraction of the strips in amplitude are (0.14±0.008)mN,(0.08±0.011)mN,(0.026±0.005)mN,(0.024±0.015)mN separately. 2. Under the preload , the contraction of the strips in frequency are (6.8±0.84)times/min(4.0±0.71)times/min(1.6±0.54)times/min(2.0±0.71)times/min separately.3. ICC-like cells do locate in guinea-pig, and mainly locate in sub-mucous membrane, along the longitude of smooth muscle bundles, between smooth muscle bundles or along the blood vessels; and the cell net is more obvious in UPJ.4. The density of ICC-like cells is different in different locations of guinea-pig upper urinary tract. There are more ICC-like cells in the UPJ and upper than that in the middle and lower, but it is reverse in the vesico-ureteral junction.Conclusion:1. The excitability is different in different locations of ureter, which indicates there may be pacemaker site in the ureter.2. The ICC-like cells do locate in guinea-pig upper urinary tract, and it is strong positive correlation between the density of ICC-like cells and smooth muscle excitability, that there may be close relationship between ICC-like cells and the function of smooth muscle contraction. So ICCs may be the pacemaker of ureter.
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