Pleumsamran A, Kim D
Department of Physiology and Biophysics, Finch University of Health Sciences Chicago Medical School, IL 60064, USA.
J Membr Biol. 1995 Dec;148(3):287-97. doi: 10.1007/BF00235046.
Arachidonic acid has been shown to activate K(+)-selective, mechanosensitive ion channels in cardiac, neuronal and smooth muscle cells. Since the cardiac G protein (GK)-gated, muscarinic K+ (KACh) channel can also be activated by arachidonic acid, we investigated whether the KACh channel was also sensitive to membrane stretch. In the absence of acetylcholine (ACh), KACh channels were not active, and negative pressure failed to activate these channels. With ACh (10 microM) in the pipette, applying negative pressure (0 to -80 mm Hg) to the membrane caused a reversible, pressure-dependent increase in channel activity in cell-attached and inside-out patches (100 microM GTP in bath). Membrane stretch did not alter the sensitivity of the KACh channel to GTP. When GK was maximally activated with 100 microM GTP gamma S in inside-out patches, the KACh channel activity could be further increased by negative pressure. Trypsin (0.5 mg/ ml) applied to the membrane caused activation of the KACh channel in the absence of ACh and GTP; KACh channel activity was further increased by stretch. These results indicate that the atrial muscarinic K+ channels are modulated by stretch independently of receptor/G protein, probably via a direct effect on the channel protein/ lipid bilayer.
花生四烯酸已被证明可激活心脏、神经元和平滑肌细胞中的钾离子选择性机械敏感离子通道。由于心脏G蛋白（GK）门控的毒蕈碱钾通道（KACh）也可被花生四烯酸激活，我们研究了KACh通道是否也对膜拉伸敏感。在没有乙酰胆碱（ACh）的情况下，KACh通道不活跃，负压也无法激活这些通道。在移液管中加入ACh（10微摩尔）后，对膜施加负压（0至 -80毫米汞柱）会导致细胞贴附式和内面向外式膜片（浴中含有100微摩尔GTP）中的通道活性出现可逆的、压力依赖性增加。膜拉伸并未改变KACh通道对GTP的敏感性。当在内面向外式膜片中用100微摩尔GTPγS使GK最大程度激活时，负压可进一步增加KACh通道活性。将胰蛋白酶（0.5毫克/毫升）施加于膜上会在没有ACh和GTP的情况下激活KACh通道；拉伸可进一步增加KACh通道活性。这些结果表明，心房毒蕈碱钾通道可通过对通道蛋白/脂质双层的直接作用，独立于受体/G蛋白而受到拉伸的调节。
