|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1994 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1993 : ¥1,700,000 (Direct Cost : ¥1,700,000)
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.