Mitogens and oncogenes can block the induction of specific voltage-gated ion channels.
Mitogens and oncogenes can block the induction of specific voltage-gated ion channels.
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DOI：
10.1126/science.2437651
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发表时间：
1987-05
期刊：
影响因子：
56.9
通讯作者：
JM Caffrey;AM Brown;Schneider
中科院分区：
文献类型：
--
作者：
JM Caffrey;AM Brown;Schneider
肌肉中电压门控离子通道的个体发生机制尚不清楚。电压门控通道的表达是否依赖于有丝分裂原的撤回和生长停滞，一般是真实的肌肉特异性基因产物的诱导，研究了在BC 3 H1肌肉细胞系膜片钳技术。分化的BC 3 H1肌细胞表达功能性Ca 2+和Na+通道，对应于骨骼肌T小管中发现的那些。然而，Ca 2+和Na+通道在有丝分裂原撤除约5天后首次检测到。为了测试细胞癌基因作为外源性生长因子的替代物是否可以阻止离子通道的表达，所述离子通道的诱导取决于有丝分裂原的撤回，通过用癌基因表达载体稳定转染来修饰BC 3 H1细胞。在SV 40启动子的控制下含有v-erbB或c-myc的表达载体延迟但不阻止功能性Ca 2+和Na+通道的出现。相反，用Val 12 c-H-ras载体转染，或c-myc与v-erbB共转染，抑制功能性Ca 2+和Na+通道的形成大于或等于4周。钾通道既不受有丝分裂培养基，也不受转染的癌基因。因此，某些癌基因对离子通道诱导的选择性作用对应于促有丝分裂培养基的抑制作用。
The mechanisms underlying the ontogeny of voltage-gated ion channels in muscle are unknown. Whether expression of voltage-gated channels is dependent on mitogen withdrawal and growth arrest, as is generally true for the induction of muscle-specific gene products, was investigated in the BC3H1 muscle cell line by patch-clamp techniques. Differentiated BC3H1 myocytes expressed functional Ca2+ and Na+ channels that correspond to those found in T tubules of skeletal muscle. However, Ca2+ and Na+ channels were first detected after about 5 days of mitogen withdrawal. In order to test whether cellular oncogenes, as surrogates for exogenous growth factors, could prevent the expression of ion channels whose induction was contingent on mitogen withdrawal, BC3H1 cells were modified by stable transfection with oncogene expression vectors. Expression vectors containing v-erbB, or c-myc under the control of the SV40 promoter, delayed but did not prevent the appearance of functional Ca2+ and Na+ channels. In contrast, transfection with a Val12 c-H-ras vector, or cotransfection of c-myc together with v-erbB, suppressed the formation of functional Ca2+ and Na+ channels for greater than or equal to 4 weeks. Potassium channels were affected neither by mitogenic medium nor by transfected oncogenes. Thus, the selective effects of certain oncogenes on ion channel induction corresponded to the suppressive effects of mitogenic medium.