〔Abstract〕 Objective To investigation of the interaction between interstitial cells of Cajal(ICCs) and connexin 43(Cx43) in bladder contraction and its significance. Methods Eighty male guinea pigs were randomly divided into blank control group, Glivec group, Gap27 group and Glivec+ Gap27 group. Four groups of guinea pigs were perfused with saline, Glivec, Gap 27, and Glivec+Gap 27 every morning for 2 months. Success of urodynamic testing model after 2 months. Bladder tissue was collected for an in vitro muscle strip test to detect muscle contraction in each group. Correlation between c-Kit and Cx43 was detected by immunofluorescence. The interaction between c-Kit and Cx43 in the bladder was further validated by qRT-PCR and Western blot. Ultrastructural changes in the muscle layer of the bladder were observed by electron microscopy. Results Urodynamics revealed increased blad-der compliance in the experimental group compared to the blank control group(P<0.05); bladder compliance increased in the Glivec + Gap27 group compared to the Glivec and Gap27 groups( P<0. 01). In vitro muscle strip experiments revealed that the frequency and tone of bladder muscle strip contractions were lower in the experimental group compared to the blank control group( P<0. 05),and that muscle strip contractions were weaker in the experimental group after administration of acetylcholine( ACH) compared to the control group( P<0. 05). Immunofluorescence showed that c-Kit was co-expressed with Cx43 on ICCs cells. qRT-PCR and Western blot suggested that the protein expression level and gene expression level of Cx43 in bladder tissues were lower after inhibition of c-Kit than in the blank control( P<0. 05); after inhibition of Cx43,the protein expression level and gene expression level of c-Kit in bladder tissues the levels of c-Kit protein expression and gene expression in bladder tissues were lower than those in the blank control group( P<0. 05). Electron microscopy revealed that the mitochondrial structure of bladder smooth muscle was disrupted after simultaneous inhibition of c-Kit and Cx43. Conclusion Cx43 is expressed on bladder ICCs and the two may be jointly involved in regulating bladder contractile function;the joint reduction of Cx43 and c-Kit may have disrupted the mitochondria of bladder smooth muscle,affecting its function and consequently bladder contractile function.