Department of Physiology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
PLoS One. 2011;6(7):e22304. doi: 10.1371/journal.pone.0022304. Epub 2011 Jul 28.
The β-adrenoceptors (β-ARs) control many cellular processes. Here, we show that β-ARs inhibit calcium depletion-induced cell contractility and subsequent cell detachment of L6 skeletal muscle cells. The mechanism underlying the cell detachment inhibition was studied by using a quantitative cell detachment assay. We demonstrate that cell detachment induced by depletion of extracellular calcium is due to myosin- and ROCK-dependent contractility. The β-AR inhibition of L6 skeletal muscle cell detachment was shown to be mediated by the β(2)-AR and increased cAMP but was surprisingly not dependent on the classical downstream effectors PKA or Epac, nor was it dependent on PKG, PI3K or PKC. However, inhibition of potassium channels blocks the β(2)-AR mediated effects. Furthermore, activation of potassium channels fully mimicked the results of β(2)-AR activation. In conclusion, we present a novel finding that β(2)-AR signaling inhibits contractility and thus cell detachment in L6 skeletal muscle cells by a cAMP and potassium channel dependent mechanism.
β-肾上腺素受体（β-AR）控制着许多细胞过程。在这里，我们表明β-AR 抑制钙耗竭诱导的细胞收缩和随后的 L6 骨骼肌细胞脱落。通过使用定量细胞脱落测定法研究了细胞脱落抑制的机制。我们证明，细胞外钙耗竭诱导的细胞脱落是由于肌球蛋白和 ROCK 依赖性收缩引起的。β-AR 抑制 L6 骨骼肌细胞脱落是通过β（2）-AR 和增加的 cAMP 介导的，但出乎意料的是，它不依赖于经典的下游效应物 PKA 或 Epac，也不依赖于 PKG、PI3K 或 PKC。然而，钾通道的抑制可阻断β（2）-AR 介导的作用。此外，钾通道的激活完全模拟了β（2）-AR 激活的结果。总之，我们提出了一个新的发现，即β（2）-AR 信号通过 cAMP 和钾通道依赖的机制抑制 L6 骨骼肌细胞的收缩，从而抑制细胞脱落。
