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

肥大细胞起源于多潜能的造血干细胞，在周围组织中分化为不同的表型，即粘膜和结缔组织类型。最近的研究发现，腹膜肥大细胞(结缔组织类型)中的离子通道与类似粘膜类型的肥大细胞(RBL-2H3)中的离子通道有很大的不同。通过体外培养小鼠骨髓细胞，在肥大细胞生长因子的存在下获得的骨髓源性肥大细胞(BMMC)具有在适当的微环境中分化为不同表型的潜能。为了了解离子通道表达在肥大细胞增殖或分化中的意义，BALB/c小鼠BMMC具有异质性电生理特征，根据20-24ﾟC时的电流活动情况，初步分为4个亚群：无电流活动的细胞(类型1)，内向整流K^+(IR_K)电流(类型2)，外向整流氯离子(OR_&lt；在第二类细胞中，膜电位因细胞外K~+浓度的升高而不同，并倾向于去极化。在第三类细胞中，静息电位随着电导的增加而超极化。因此，IR_K和OR_&lt；即使在1型细胞中，我们也观察到依赖温度的外向电流(初步观察)，这暗示细胞内代谢变化可能调节BMC中通道的激活。我们认为细胞周期、分化阶段和细胞内代谢的差异可能是导致BMC离子通道活性异质性的原因。对单个离子通道调节机制的研究正在进行中。

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.