Interstitial cells of Cajal (ICC) are believed to participate in urethral neurotransmission and it was proposed that direct coupling of ICC and smooth muscle cells (SMC) through Gap Junctions (GJ) is involved, although this still remains unclear. Hence, we have investigated the distribution of different connexins (Cx 43, Cx40 and Cx37) in the sheep and rat urethra, as well as their possible role in neurotransmission. Conventional PCR confirmed that three Cxs are expressed in the urethra. Moreover, both Cx43 and Cx37-immunoreactivity (-ir) was present in SMC, ICC and the urothelium, although Cx37-ir was significantly weaker and Cx40-ir was limited to the endothelium. While these results indicate that GJ intercellular communication could occur between SMC and ICC, neither the contractile (noradrenergic) nor the relaxant (nitrergic) responses of the rat and sheep urethra to electrical field stimulation were significantly modified by two different GJ Inhibitors: 18α-Glycyrrhetinic acid and a cocktail of Cx mimetic peptides (Cx43Gap 26, Cx37, Cx43Gap 27 and Cx40Gap 27). By contrast, contractions induced by high K+ were effectively reduced by both blockers, evidence that they effectively inhibit intercellular communication. These results indicate that GJ are not implicated in urethral neurotransmission, although the question of whether ICC modulate neurotransmission through some other mechanism remains to be determined.
- Interstitial cells of Cajal
- nitric oxide
- Copyright © 2010, American Journal of Physiology - Renal Physiology