Li Hongliang, Shin Sung Eun, Kim Hye Won, Kim Han Sol, Jung Won-Kyo, Ha Kwon-Soo, Han Eun-Taek, Hong Seok-Ho, Choi Il-Whan, Bae Young Min, Firth Amy L, Bang Hyoweon, Park Won Sun
Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea.
Pharmacology. 2016;98(5-6):220-227. doi: 10.1159/000447745. Epub 2016 Jul 21.
We examined the effects of the Rho-associated protein kinase (ROCK) inhibitor Y-27632 on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells using the whole-cell patch clamp technique. Y-27632 reduced the amplitude of the Kv current in a concentration-dependent manner, with an IC50 of 0.87 ± 0.06 μmol/l and a Hill coefficient of 1.48 ± 0.06. Y-27632 did not affect the steady-state activation or inactivation curves, suggesting that the drug does not affect the voltage sensitivity of Kv channels. Another ROCK inhibitor, H-1152, did not affect the Kv current and had no significant effect on the Y-27632-induced inhibition of Kv channels, indicating that the inhibitory effect of Y-27632 on the Kv current is independent of ROCK signaling. From these results, we conclude that Y-27632 inhibits the Kv channel current in a dose-dependent and ROCK signaling-independent manner.
我们使用全细胞膜片钳技术研究了Rho相关蛋白激酶（ROCK）抑制剂Y-27632对兔冠状动脉平滑肌细胞中电压依赖性钾离子（Kv）通道的影响。Y-27632以浓度依赖性方式降低Kv电流的幅度，半数抑制浓度（IC50）为0.87±0.06μmol/l，希尔系数为1.48±0.06。Y-27632不影响稳态激活或失活曲线，表明该药物不影响Kv通道的电压敏感性。另一种ROCK抑制剂H-1152不影响Kv电流，对Y-27632诱导的Kv通道抑制也无显著影响，表明Y-27632对Kv电流的抑制作用独立于ROCK信号传导。根据这些结果，我们得出结论，Y-27632以剂量依赖性和ROCK信号传导非依赖性方式抑制Kv通道电流。
