Physiology and Biophysics, 301 Cary Hall, SUNY at Buffalo, Buffalo, NY 14214, USA.
Neurosci Lett. 2010 Sep 6;481(2):115-9. doi: 10.1016/j.neulet.2010.06.066. Epub 2010 Jun 26.
GsMTx4, a peptide inhibitor for mechanosensitive ion channels (MSCs), promoted neurite outgrowth from PC12 cells in the presence of NGF in a dose-dependent manner between 5 and 100 microM peptide. Enhanced neurite growth required >12 h of peptide exposure in cells grown with NGF. Adsorption of GsMTx4 to serum proteins in the media lowered the free peptide concentration of 100 microM to a free concentration of 5 microM, a concentration shown to completely inhibit MSCs in the patch clamp assay. Outside-out patches from PC12 cells grown in NGF had mechanically activated cation channels that were reversibly inhibited by GsMTx4. These results are similar to those observed by Gomez and co-workers in Xenopus spinal cord. The inhibition of mechanosensitive channels by GsMTx4 may be a useful approach to accelerate regeneration of neurons in neurodegenerative diseases and spinal cord injury.
GsMTx4 是一种机械敏感离子通道（MSCs）的肽类抑制剂，在存在 NGF 的情况下，它能以剂量依赖的方式促进 PC12 细胞的轴突生长，肽浓度在 5 到 100 μM 之间。增强的轴突生长需要在有 NGF 的细胞中暴露于肽 12 小时以上。GsMTx4 吸附到培养基中的血清蛋白降低了 100 μM 游离肽的浓度到 5 μM 的游离浓度，该浓度在膜片钳实验中显示能完全抑制 MSCs。在 NGF 中生长的 PC12 细胞的外向型膜片上有机械激活的阳离子通道，可被 GsMTx4 可逆抑制。这些结果与 Gomez 及其同事在非洲爪蟾脊髓中观察到的结果相似。GsMTx4 对机械敏感通道的抑制可能是一种加速神经退行性疾病和脊髓损伤中神经元再生的有用方法。
