DYNAMIC GAP JUNCTIONAL COMMUNICATION - A DELIMITING MODEL FOR TISSUE RESPONSES

Gap junctions are aqueous intercellular channels formed by a diverse C lass of membrane-spanning proteins, known as connexins. These aqueous pores provide partial cytoplasmic continuity between cells in most tis sues, and are freely permeable to a host of physiologically relevant s econd messenger molecules/ionic species (e.g., Ca2+, IP3, cAMP, cGMP). Despite the fact that these second messenger molecules/ionic species have been shown to alter junctional patency, there is no clear basis f or understanding how dynamic and transient changes in the intracellula r concentration of second messenger molecules might modulate the exten t of intercellular communication among coupled cells. Thus, we have mo dified the tissue monolayer model of Ramanan and Brink (1990) to accou nt for both the up-regulatory and down-regulatory effects on junctions by second messenger molecules that diffuse through gap junctions. We have chosen the vascular wall as our morphological correlate because o f its anisotropy and large investment of gap junctions. The model allo ws us to illustrate the putative behavior of gap junctions under a var iety of physiologically relevant conditions. The modeling studies demo nstrated that transient alterations in intracellular second messenger concentrations are capable of producing 50-125% changes in the number of cells recruited into a functional syncytial unit, after activation of a single cell. Moreover, the model conditions required to demonstra te such physiologically relevant changes in intercellular diffusion am ong coupled cells are commonly observed in intact tissues and cultured cells.