Effects of Mechanical Stretch on Interstitial Cells of Cajal in Guinea Pig Bladder

Abstract

C-kit positive interstitial cells of Cajal (ICCs) play an important role in the regulation of the smooth muscle motility. In this study, we investigated the mechanical sensitivity of ICCs in guinea pig bladder and their possible relationship with detrusor overactivity (DO). Stretch load was performed in vivo in DO models produced by 4 wk of partial bladder outlet obstruction (PBOO). Number and morphology of ICCs were examined using a specific ICC marker, c-kit, immunochemistry staining. The spontaneous and stretch-induced calcium transients (SICT) of ICCs were investigated in cells cultured onto flexible silicone membranes preloaded with the Ca(2+) indicator fluo-4AM in vitro. C-kit positive ICCs were mainly located along and between bladder smooth muscle bundles. ICCs in DO bladders displayed more lateral branching with mutual connections. The number of c-kit positive bladder ICCs was increased in the DO group compared with the control group (n = 50, P < 0.05). Cultured ICCs from DO bladders showed spontaneous calcium waves with higher frequency and lower amplitude than those from control bladders (n = 15, P < 0.05). Significant SICT were detected in cultured bladder ICCs. SICT generated in ICCs from DO were more likely to transfer to adjacent smooth muscle cells through cell membrane connection than ICCs from control bladders. Long-term overload tension following PBOO caused changes in morphology, quantity and spontaneous calcium transients of ICCs in guinea pig bladder. Mechanical sensitivity and interaction with SMC of ICCs may contribute to the mechanosensitive conductances in bladder regulation, and may play a role in the pathogenesis of DO.