GAP JUNCTIONS IN VASCULAR SMOOTH MUSCLE--GROWTH CONTROL

描述：Burt 博士，差距文献的长期贡献者 连接门控和调节，提出了详细分析 间隙连接耦合对有丝分裂刺激的反应（急性和 慢性）在三种不同的细胞系中。 这些调查的基础 PI 的一个令人兴奋的发现与一般教条相反 细胞增殖过程中细胞间耦合减少。 相反，她发现，比较增殖和增长停滞 A7r5 细胞，通过染料扩散测量的耦合减少，但电 耦合增加。 这一变化与 单通道电导的分布（150pS 通道和 70pS 通道的减少）以及两者的 RNA 水平的反向变化 这些细胞中表达的主要连接蛋白（即 Cx40 增加并减少 43）。 由这些数据得出的假设是 增殖状态可能需要保持电耦合，但会抑制 更大的代谢物和信使的交换，并通过以下方式实现这一点 具有不同渗透选择性的连接蛋白的差异表达（它是 假设，在没有证实的情况下，阴离子偏好有利于 相关信使系统）。 该提案最终旨在 定义间隙连接在相关增殖反应中的作用 患有动脉粥样硬化。 为此，PI 部分描述了 三种细胞系统——A7r5 细胞、原代平滑肌细胞 (SMC) 和 转染 HeLa 细胞——并建立血清剥夺生长条件 阻滞以及 PDGF 和 ox-LDL 促有丝分裂刺激。

DESCRIPTION: Dr. Burt, a long contributor to the literature on gap junctional gating and regulation, proposes a detailed analysis of the response of gap junctional coupling to mitogenic stimuli (both acute and chronic) in three different cell lines. The basis of these investigations is an exciting finding by the PI that runs contrary to the general dogma that intercellular coupling is decreased during cellular proliferation. Instead, she has found that, comparing proliferating and growth arrested A7r5 cells, coupling as measured by dye spread decreases, but electrical coupling increases. This change is coincident with a change in the distribution of single channel conductances (increase in 150pS channel and decrease in 70pS channel) and inverse changes in the RNA levels of the two major connexins expressed in these cells (i.e. increase in Cx40 and decrease in 43). The hypothesis that arises from these data is that the proliferative state may need to retain electrical coupling, but depresses the exchange of larger metabolites and messengers, and achieves this through differential expression of connexins with varying permselectivities (it is assumed, without substantiation, that anionic preference would favor the relevant messenger system). Ultimately the proposal is directed towards defining a role for gap junctions in the proliferative responses associated with Atherosclerosis. Towards this end, the PI has partially characterized three cell systems--A7r5 cells, primary Smooth Muscle Cells (SMCs), and transfected HeLa cells--and established conditions for serum deprived growth arrest and PDGF and ox-LDL mitogenic stimulation.