Fast-to-slow transformation and nuclear import/export kinetics of the transcription factor NFATc1 during electrostimulation of rabbit muscle cells in culture

被引:49
作者
Kubis, HP [1 ]
Scheibe, RJ [1 ]
Meissner, JD [1 ]
Hornung, G [1 ]
Gros, G [1 ]
机构
[1] Hannover Med Sch, Zentrum Physiol, D-30623 Hannover, Germany
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2002年 / 541卷 / 03期
关键词
D O I
10.1113/jphysiol.2002.017574
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Contractile activity imposed by chronic electrical stimulation of a primary skeletal muscle cell culture grown on microcarriers over several days led to an increase of slow myosin heavy chain I (MHCI) and a decrease of fast MHCII expression at mRNA and protein levels, indicating an ongoing fast-to-slow transformation. Only patterns with periods of continuous stimulation of greater than or equal to 5 min in a 45 min cycle were capable of inducing a fibre type transformation, and this was independent of the applied stimulation frequency over the range 1-10 Hz. We have shown before that the calcineurin-NFATc1 signalling pathway is indispensable in mediating MHCI upregulation during fibre type transformation. Therefore, subcellular localization of NFATc1 was studied immunocytochemically. This revealed that only one stimulation train lasting for greater than or equal to 5 min was sufficient to induce nuclear import of this factor, which was about complete after 20 min of continuous stimulation. For both induction of NFATc1 import and MHCI mRNA upregulation, the minimum stimulation interval of greater than or equal to 5 min was sufficient and stimulation frequency was not crucial between I and 10 Hz. Repetition of stimulation cycles, with pauses (less than or equal to 40 min) shorter than the time required for complete export of NFATc1, led to an accumulation of NFATc1 in the nuclei with each cycle and thus to an amplification of the transformation signal during extended periods of electrostimulation. The temporal behaviour of NFATc import/export appears to determine the effectiveness of various electrostimulation protocols in inducing fast-to-slow fibre transformation.
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页码:835 / 847
页数:13
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