Pribnow D, Johnson-Pais T, Bond C T, Keen J, Johnson R A, Janowsky A, Silvia C, Thayer M, Maylie J, Adelman J P
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, USA.
Muscle Nerve. 1999 Jun;22(6):742-50. doi: 10.1002/(sici)1097-4598(199906)22:6<742::aid-mus11>3.0.co;2-1.
Skeletal muscle becomes hyperexcitable following denervation and when cultured in the absence of nerve cells. In these circumstances, the bee venom peptide toxin apamin, a blocker of small-conductance calcium-activated potassium (SK) channels, dramatically reduces the hyperexcitability. In this report, we show that SK3 channels are expressed in denervated skeletal muscle and in L6 cells. Action potentials evoked from normal innervated rat skeletal muscle did not exhibit an afterhyperpolarization, indicating a lack of SK channel activity; very low levels of apamin binding sites, SK3 protein, or SK3 mRNA were present. However, denervation resulted in apamin-sensitive afterhyperpolarizations and increased apamin binding sites, SK3 protein, and SK3 mRNA. Cultured rat L6 myoblasts and differentiated L6 myotubes contained similar levels of SK3 mRNA, although apamin-sensitive SK currents and apamin binding sites were detected only following myotube differentiation. Therefore, different molecular mechanisms govern SK3 expression levels in denervated muscle compared with muscle cells differentiated in culture.
骨骼肌在去神经支配后以及在无神经细胞的情况下培养时会变得过度兴奋。在这些情况下，蜂毒肽毒素蜂毒明肽（一种小电导钙激活钾通道（SK）的阻滞剂）可显著降低这种过度兴奋性。在本报告中，我们表明SK3通道在去神经支配的骨骼肌和L6细胞中表达。正常神经支配的大鼠骨骼肌诱发的动作电位未表现出超极化后电位，表明缺乏SK通道活性；存在极低水平的蜂毒明肽结合位点、SK3蛋白或SK3 mRNA。然而，去神经支配导致了对蜂毒明肽敏感的超极化后电位，并增加了蜂毒明肽结合位点、SK3蛋白和SK3 mRNA。培养的大鼠L6成肌细胞和分化的L6肌管含有相似水平的SK3 mRNA，尽管仅在肌管分化后才检测到对蜂毒明肽敏感的SK电流和蜂毒明肽结合位点。因此，与培养中分化的肌肉细胞相比，去神经支配的肌肉中SK3表达水平受不同的分子机制调控。
