Mitogenic factors regulate ion channels in Schwann cells cultured from newborn rat sciatic nerve.
Mitogenic factors regulate ion channels in Schwann cells cultured from newborn rat sciatic nerve.
复制标题
有丝分裂因子调节从新生大鼠坐骨神经培养的雪旺细胞中的离子通道。
DOI：
10.1113/jphysiol.1993.sp019872
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Chiu,SY
中科院分区：
文献类型：
--
作者：
Wilson,GF;Chiu,SY
1.在从新生大鼠坐骨神经培养的许旺细胞中进行膜片钳研究，以确定有丝分裂原对电压门控电流的影响，而不受轴突接触和体内存在的髓鞘的混杂影响。使用[3 H]胸苷掺入试验评估各种雪旺细胞电流与增殖的相关性。2.用已知的有丝分裂原，即轴突片段（AF），髓鞘片段（MF），或神经胶质生长因子与毛喉素（GGF+F）的组合处理培养的施万细胞，增加延迟整流钾（K+）和钠（Na+）电流的幅度。3.在对照和有丝分裂原处理的细胞中，净外向电流的大小清楚地反映了细胞增殖反应的大小。4. K+通道阻断剂季铵离子，四丁基铵（TBuA），四戊基铵（TPeA）和四己基铵（THeA），但不是Na+通道阻断剂河豚毒素（TTX），以剂量依赖性方式减少增殖，为K+通道在雪旺细胞增殖中的作用提供了进一步的证据。5.在对照和丝裂原处理的细胞中均观察到电压门控氯（Cl-）电流。向培养基中添加Cl-通道阻断剂4-乙酰氨基-4 '-异氰酸基芪-2，2'-二磺酸盐（SITS）或4，4 '-二异硫氰酸基芪-2，2'-二磺酸盐（DIDS）可增强增殖。6.在离子替代实验中，通过增加培养基中的K+浓度和加入哇巴因，探讨了许旺细胞静息电位的可能中介作用。这两种操作均抑制雪旺细胞有丝分裂。7.功能性离子通道在体外的表达与先前描述的雪旺细胞在体内的比较表明，在雪旺细胞的膜片段有丝分裂原和它们的完整的对应物方面的调节离子通道的差异。MF上调功能性通道的数量，而体内髓鞘（或与其存在相关的因子）的加工似乎下调通道表达，在髓鞘形成许旺细胞的细胞索马。此外，轴突接触可能需要功能性内向整流钾通道的正常表达。
1. Patch clamp studies were carried out in Schwann cells cultured from newborn rat sciatic nerve to determine the effects of mitogens on voltage‐gated currents without the confounding influences of axonal contact and myelin present in vivo. The relevance of the various Schwann cell currents to proliferation was assessed using assays of [3H]thymidine incorporation. 2. Treatment of cultured Schwann cells with known mitogens, namely axon fragments (AF), myelin fragments (MF), or glial growth factor in combination with forskolin (GGF+F), increased the magnitudes of delayed rectifying potassium (K+) and sodium (Na+) currents. 3. In both control and mitogen‐treated cells, the magnitude of net outward current paralleled clearly the magnitude of the cells' proliferative response. 4. The K+ channel‐blocking quaternary ammonium ions, tetrabutylammonium (TBuA), tetrapentylammonium (TPeA) and tetrahexylammonium (THeA), but not the Na+ channel blocker tetrodotoxin (TTX), reduced proliferation in a dose‐dependent fashion offering further evidence for a role for K+ channels in Schwann cell proliferation. 5. Voltage‐gated chloride (Cl‐) currents were observed in both control and mitogen‐treated cells. Addition of the Cl‐ channel blockers, 4‐acetamido‐4'‐isocyanatostilbene‐2,2'‐disulphonate (SITS) or 4,4'‐diisothiocyanatostilbene‐2,2'‐disulphonate (DIDS), to the culture media enhanced proliferation. 6. The possible intermediary role of the Schwann cell resting potential was explored in ion substitution experiments by increasing the K+ concentration of the media and by adding ouabain. Both manipulations inhibited Schwann cell mitosis. 7. Comparison of the expression of functional ion channels in vitro with that previously described for Schwann cells in vivo suggests a difference in the Schwann cell response to the membrane fragment mitogens and their intact counterparts in regard to the regulation of ion channels. MF up‐regulates the number of functional channels, whereas the elaboration of myelin (or a factor related to its presence) in vivo appears to down‐regulate channel expression, at the cell soma of myelinating Schwann cells. In addition, axonal contact may be required for normal expression of functional inwardly rectifying K+ channels.