Lo Yi-Ching, Yang Su-Rong, Huang Mei-Han, Liu Yen-Chin, Wu Sheng-Nan
Department and Graduate Institute of Pharmacology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Life Sci. 2005 Apr 1;76(20):2275-86. doi: 10.1016/j.lfs.2004.09.036. Epub 2005 Jan 27.
The effects of chromanol 293B on ion currents in rat embryonic heart-derived H9c2 cells were investigated in this study. Chromanol 293B suppressed the amplitude of delayed rectified K+ current (I(K)) in a concentration-dependent manner. The IC50 value for chromanol 293B-induced inhibition of I(K) was 8 microM. The I(K) present in these cells, the electrical properties of which resembled those for the Kv2.1-related K+ current, was sensitive to inhibition by quinidine or dendrotoxin, yet not by pandinotoxin-Kalpha, E-4031 or apamin. Chromanol 293B reduced the activation time constant of I(K) and the effective gating charge of this channel. However, little or no modification in the steady-state inactivation of I(K) in response to long-lasting conditioning pulses could be demonstrated in the presence of chromanol 293B. These results clearly demonstrate that chromanol 293B can effectively interact with the K+ channel functionally expressed in H9c2 myoblasts. The chromanol 293B-induced inhibition of these channels could primarily be attributed to open channel block.
本研究考察了色满醇293B对大鼠胚胎心脏来源的H9c2细胞离子电流的影响。色满醇293B以浓度依赖的方式抑制延迟整流钾电流（I(K)）的幅度。色满醇293B诱导I(K)抑制的IC50值为8 microM。这些细胞中存在的I(K)，其电特性类似于与Kv2.1相关的钾电流，对奎尼丁或树眼镜蛇毒素敏感，但对潘地毒素-Kalpha、E-4031或蜂毒明肽不敏感。色满醇293B缩短了I(K)的激活时间常数和该通道的有效门控电荷。然而，在色满醇293B存在的情况下，几乎没有或无法证明对I(K)的稳态失活有任何改变，这是由于长时间的预处理脉冲引起的。这些结果清楚地表明，色满醇293B可以有效地与H9c2成肌细胞中功能性表达的钾通道相互作用。色满醇293B对这些通道的抑制作用主要归因于开放通道阻断。
