DYNAMIC GAP JUNCTIONAL COMMUNICATION - A DELIMITING MODEL FOR TISSUE RESPONSES
DYNAMIC GAP JUNCTIONAL COMMUNICATION - A DELIMITING MODEL FOR TISSUE RESPONSES
复制标题
DOI：
10.1016/s0006-3495(94)80605-8
复制
发表时间：
1994-09-01
影响因子：
3.4
通讯作者：
RAMANAN, SV
中科院分区：
文献类型：
--
作者：
CHRIST, GJ;BRINK, PR;RAMANAN, SV
间隙连接是由多种跨膜蛋白（称为连接蛋白）形成的水性细胞间通道。这些水孔在大多数组织中的细胞之间提供部分细胞质连续性，并且可自由渗透大量生理相关的第二信使分子/离子种类（例如 Ca2+、IP3、cAMP、cGMP）。尽管这些第二信使分子/离子种类已被证明可以改变连接的通畅性，但没有明确的基础来理解第二信使分子的细胞内浓度的动态和瞬时变化如何调节偶联细胞之间的细胞间通讯的程度。因此，我们修改了 Ramanan 和 Brink (1990) 的组织单层模型，以解释通过间隙连接扩散的第二信使分子对连接的上调和下调作用。我们选择血管壁作为我们的形态相关物，因为它的各向异性和间隙连接的大量投入。该模型使我们能够说明间隙连接在各种生理相关条件下的假定行为。建模研究表明，在激活单个细胞后，细胞内第二信使浓度的瞬时变化能够使招募到功能合胞体单位的细胞数量发生 50-125% 的变化。此外，证明偶联细胞之间细胞间扩散的这种生理相关变化所需的模型条件通常在完整组织和培养细胞中观察到。
Gap junctions are aqueous intercellular channels formed by a diverse Class of membrane-spanning proteins, known as connexins. These aqueous pores provide partial cytoplasmic continuity between cells in most tissues, and are freely permeable to a host of physiologically relevant second 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 for understanding how dynamic and transient changes in the intracellular concentration of second messenger molecules might modulate the extent of intercellular communication among coupled cells. Thus, we have modified the tissue monolayer model of Ramanan and Brink (1990) to account 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 of its anisotropy and large investment of gap junctions. The model allows us to illustrate the putative behavior of gap junctions under a variety of physiologically relevant conditions. The modeling studies demonstrated 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 demonstrate such physiologically relevant changes in intercellular diffusion among coupled cells are commonly observed in intact tissues and cultured cells.