| Backgroud and Objective:In the urinary system, ureter acts as a bridge, connecting the kidneys and bladder. Urine produced in the kidneys is pushed to the bladder in the form of pellets via the ureters. Ureter has excitability, under normal physiological conditions, ureter may generate slow wave similar to gastrointestinal peristalsis, about 7-8 times per minute, pushing forward the urine. In vitro denervation or after spinal anesthesia, ureteral peristalsis has not disappeared, a phenomenon that could indicate spontaneous excitatory in ureter may similar to its in heart or gastrointestinal system, the spontaneous electric activity originated. In clinic, ureter proper function is closely related to a series of power-related urinary tract or congenital ureter related diseases, such as functional ureteral obstruction, congenital ureteropelvic junction obstruction, congenital megaureter and vesicoureteral reflux and so on. Also part of the kidney transplant patients, if their pelvis or calyx damage, there will be no urinary symptoms after surgery. While Patients undergoing kidney transplantation together with the renal pelvis or calyx, mostly spontaneous peristalsis of their ureters recover faster. The former mainly because of the ureteral peristalsis diminished or disappeared dynamic obstruction caused further easily lead to infection and formation of uremia. Thus, the system and in-depth study of spontaneous ureteral peristalsis excitability Origin and Inner regulatory mechanism will play an important guiding significance for a variety of basic research and clinical treatment of ureteral related diseases.HCN channel has its special physiological characteristics, and it was originally found in the heart and neurons. The other channels are mostly activated in the depolarization phase, while HCN channels can be activated over the intensification stage, and further lead to inner-selective cation flow. HCN channel is a non-selective cation channels that can be regulated by voltage and cyclic adenosine monophosphate. HCN channel has four subtypes, and its generated Ih current is generally considered to be an important symbol of pacemaker cells. HCN channel also could stable membrane potential of excitable cells, involved in the regulation of self-discipline, involved in the regulation of neurotransmitter release, involved in various feeling, expression of visual, auditory signal integrity and other physiological functions. As the slow wave Pacemaker channel, HCN channel mainly expressed in the mammalian heart and nervous system, and its important role in cardiac pacing and nerve activity has been clear. In recent years, other organs, tissues and cells of human body, such as the gastrointestinal tract, bladder, whether the Ih current generated by HCN channel is the main component of the formation of the starting point has been becoming a sustained research focus.In recent years, Researchers in several countries have found the HCN channels in the guinea pig renal medullary collecting systems, and the urinary bladder of rats or human beings, and conducted related in-depth research. Also has the spontaneous excitement capacity, whether there is pacemaker channel HCN existed in the ureters of huamn beings? If there is, which role does it play? For this question we conducted a preliminary study. In our study, with using the methods of molecular biology and morphology, the expression and distribution of HCN channels and its subtypes in the human ureter were observed. And a preliminary judgment was made by learning from the functional role of HCN channels playing in human ureteral spontaneous peristalsis. The results show that HCN channels also exists in the human ureters, while it may play an important role in the spontaneous contraction of human ureters.Meterials and Methods:12 normal cases of isolated ureter specimens of patients was collected after surgery because of kidney tumors or cysts row nephrectomy. The patients were all confirmed they had not been put special treatment, chemotherapy and immune therapy before surgery. The HCN channel blocker ZD7288 was applied to ureteral smooth muscle strips in vitro experiments. Then observed the contraction frequency and amplitude changes in muscle strips. Use human intestinal tissues as a positive control, reverse transcription-polymerase chain reaction, Western-Blotting method and immunohistochemical techniques were taken to detect the expression and distribution of HCN channel in the human ureter from the gene and protein levels.Results:1. All four m RNA of the HCN channel subtypes could be detected in human ureteral tissue by applying RT-PCR, in which the expression of HCN4 isoforms is relatively obvious; with using Western-Blotting method and immunohistochemistry, the protein of all HCN1-4 channels were confirmed in human ureteral tissue, and the expression of each subtype in the ureter epithelium and smooth muscle layer is relatively higher than that of other layers.2. Incubated at the Kreb’s solution for 30 min, stable spontaneous contraction of the muscle strips appear, its contraction amplitude(1.531 ± 0.306) g, frequency of(1.609 ± 0.204) beats / min, after adding HCN channel blocker ZD7288, contraction amplitude becomes(1.402 ± 0.256) g, frequency of(0.469 ± 0.034) beats / min, P values <0.01 were significantly different.Conclusions:1. HCN channel exists in the Normal human ureters.2. HCN channel can affect the spontaneous excitatory and contraction of human ureter and it may play an important role in human spontaneous contraction of the ureter. |
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