Relationship Between Excitability And Detrusor Instability

Background: Detrusor instability (DI) is one of the most common micturation dysfunction diseases in clinic, mainly appears to be urinary frequency, urinary urgency and stress incontinence et al. The pathogenesis causing DI is still unclear, while somebody thinks the pathological change of nervous system is the main cause of detrusor instability, but the antagonist and agonist of different nerves in the treatment of detrusor instability are not satisfactory. Detrusor is a kind of excitable tissue, so the excitability of detrusor must play a key role in the occurring of detrusor instability, but there were few reports about the excitability of detrusor. The objective of this study is to investigate the mechanism of detrusor instability, especially the relationship between the excitability and detrusor instability, and the effects of potassium and calcium on detrusor excitability.Materials and Methods: Idiopathic (IDI), bladder outlet obstruction (BOO) and spinal cord transection (SCT) caused detrusor instability model were established in female Wistar rats by operation and urodynamics. Pathological changes in detrusor were studied by light and electronic microscope. The spontanouse contraction frequency and strength of detrusor strip were measured: â‘ The minimums tension while spontaneous contraction occurred was recorded; â‘¡The contraction frequency of strip at fixed tension (1.0g) was recorded; â‘¢The effect of carbachol (muscarinic receptor agonist) and atropine (muscarinic receptor antagonist) on the contraction frequency of strip at fixed tension (1.0g) were recorded. The blind whole cell patch clamp recording technique for detrusor bladder smooth muscle cell (DSMC) in bladder muscle slice was performed. The resting membrane potential (RMP), input resistance (IR) and action potential (AP) were recorded and compared. The potassium currents of DSMC were recorded and the components were analyzed. The changes of the currents in DI groups were evaluated. The expressions of all the kinds of potassium channels were detected by RT-PCR technique. The changes of the potassium channels' expression in DI groups were evaluated. The concentration of free Ca2+ in DSMC was measured by laser scanning confocal microscope (LSCM). The calcium currents of DSMC were recorded and the components were analyzed. The changes of calcium currents in DI were evaluated. Expressions of L and T type of calcium channels were detected by RT-PCR. The changes of the calcium channels' expression in DI groups were evaluated.Results and discussion: The detrusor smooth muscle cells appeared hypertrophy, more gap junctions and protrusion junctions were found. Detrusor of all groups contracted at definite tension. DI strips contracted in lower tension and had the higher contraction frequency than that of stable. There were no obviously changes while the detrusor strips mustarded by muscarinic receptor antagonist and agonist, which means the excitability of detrusor is determined mainly by myogenic factors instead of muscarinic receptor. DSMCs with detrusor instability groups had the higher RMP and IR. AP of DSMC with detrusor instability groups could be evoked with lower depolarized stimulation compared with control. The duration of AP was prolonged in DI groups. The potassium current of DSMC was composed by many kinds of currents. Delayed rectifying potassium current and Ca2+ activated potassium current were the main parts. Delayed rectifying potassium current in DSMC with DI was higher than that of control. There were many kinds of potassium channels expressed in Wistar rat detrusor, such as Kv 1.2, 1.3, 1.4, 1.5, 2.1, 3.2, and 4.2, BKCa, SKCa and KATP. The expression of Kv2.1 in BOO and SCI were much lower than that of control, and the expression of KATP in BOO and SCI were much higher than that of control. Potassium channels can affect the excitability of cells, so changes of function and expression of potassium channel may be one of the cause in the occurring of DI. The calcium current of DSMC was composed of many kinds of currents, t...