BERKELEY, CA (UroToday.com) - A connexin is a special type of protein composed of an assembly of six subunits that are called connexins. A connexon of one cell is joined to that of an adjacent cell to form an intercellular channel consisting of 12 connexin subunits. Clusters of intercellular channels are known as a gap junction because of the minute extracellular "gap" that separates the apposed plasma membranes. Each intercellular channel provides an axial channel that interconnects the cytoplasm of the apposed cell directly and permits the passage of ion and other small molecules between adjacent cells. Connexin (Cx) expression is prominent in myofibroblast-like cells, supposedly involved in afferent signaling pathways of the bladder. Cx43 is expressed in the myofibroblast cells beneath the urothelium, whereas Cx45, the other major connexin subtype expressed in the detrusor, is not. Their position directly beneath the urothelium suggests they are a link between urothelial ATP signaling during bladder filling and afferent Ad-fibre stimulation for coordination of bladder tone and initialization of the micturition reflex.

Jochen Neuhaus and colleagues from Leipzig and Tubingen, Germany looked at bladder tissue expression of Cx43 and Cx45 in patients with severe idiopathic urge symptoms, interstitial cystitis, and carcinoma in situ. They found that Cx43 is expressed at low levels in normal detrusor. They noted significant up-regulation of Cx43 in women with urge symptoms, implying increased coupling between detrusor smooth muscle cells. They could not detect differences between the groups in Cx43 expression in the myofibroblast layer, but there was some increase in Cx45 in these cells. This supports the idea of an involvement of the sensory signaling system of the bladder in the pathophysiology. The pathophysiology of urgency appears distinct from that of the unstable bladder and other forms of incontinence.

BJU International 2005 September; 96:670-676