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Ion channels and the regulatory mechanisms in different phenotypic mast cells derived from bone marrow hematopoietic stem cells

骨髓造血干细胞不同表型肥大细胞的离子通道及调控机制

基本信息

批准号：
05670052
负责人：
KUNO Miyuki
金额：
$ 1.41万
依托单位：
OSAKA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Mast calls originate from multipotential hematopoietic stem cells and differentiate into different phenotypes, the mucosal and connective tissue types, in the peripheral tissues.Recent studies noted that ion channels in peritoneal mast cells (the connective tissue type) and a tumor analog of the mucosal type mast cells (RBL-2H3), were quite different.Bone marrow-derived mast cells (BMMC) obtained by an in vitro culture of mouse bone marrow cells in the presence of mast cell growth factors have a potency to differentiate into the different phenotypes in appropriate microenvironments.In order to understand significance of ion channel expression in either proliferation or differentiation of mast cells, membrane currents of mouse (Balb/c) BMMC were recorded under the whole cell clamp configuration.BMMC had a heterogeneous electrophysiological profile and were tentatively classified into four subpopulations according to the current activities at 20-24ﾟC : Cells with no current activity (type 1), inwardly rectifying K^+ (IR_K) currents (type 2), outwardly rectifying Cl^- (OR_<Cl>) currents (type 3) and inward plus outward currents (type 4) (Kuno, et al., in press).In the type 2 cells, the membrane potential varied among cells and tended to depolarize by elevating the external K^+ concentration.In the type 3 cells, the resting potential was hyperpolarized in association with an increase in the conductance.Thus both the IR_K and OR_<Cl> channels are likely to contribute to the regulation of the membrane potential.We also observed temperature-dependent outward currents even in the type 1 cells (preliminary observations), which implicates that intracellular metabolic changes may regulate activation of channels in BMMC.We suggest that differences in cell cycles, stages of differentiation and intracellular metabolisms may underlie the heterogeneity in ion channel activities in BMMC.Studies on regulatory mechanisms of individual ion channels are going on.

肥大细胞来源于多潜能造血干细胞，在外周组织中分化为粘膜型和结缔组织型等不同的表型。（结缔组织型）和粘膜型肥大细胞的肿瘤类似物（RBL-2 H3），骨髓源性肥大细胞（BMMC）通过在肥大细胞生长因子存在下体外培养小鼠骨髓细胞获得的具有分化成不同表型的潜能，为了了解离子通道表达在肥大细胞增殖或分化中的意义，在全细胞钳夹配置下记录小鼠（Balb/c）BMMC的膜电流。BMMC具有异质性电生理特征，并根据20-24 ℃下的电流活性初步分为四个亚群：无电流活动（1型）、内向整流K^+（IR_K）电流（2型）、外向整流Cl^-（OR_<Cl>）电流（3型）和内向加外向电流（4型）的细胞（Kuno，et al.，在2型细胞中，膜电位在细胞间存在差异，并随着外部K^+浓度的升高而趋于降低。在3型细胞中，静息电位超极化与电导的增加有关。因此IR_K和OR_<Cl>通道可能都参与了膜电位的调节。我们还观察到温度对膜电位的影响。依赖性外向电流甚至在1型细胞中（初步观察），这意味着细胞内代谢的变化可能调节BMMC通道的激活。我们认为，细胞周期的差异，BMMC的分化阶段和细胞内代谢可能是BMMC离子通道活性异质性的基础。单独的离子通道在运行。