Premium
The calmodulin inhibitor N ‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalene sulphonamide directly blocks human ether à ‐go‐go‐related gene potassium channels stably expressed in human embryonic kidney 293 cells
Author(s) -
Zhang XiaoHua,
Jin ManWen,
Sun HaiYing,
Zhang Shetuan,
Li GuiRong
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00916.x
Subject(s) - herg , calmodulin , hek 293 cells , potassium channel , chemistry , depolarization , patch clamp , potassium channel blocker , ion channel , biophysics , biochemistry , biology , gene , enzyme , receptor
BACKGROUND AND PURPOSE N ‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalene sulphonamide (W‐7) is a well‐known calmodulin inhibitor used to study calmodulin regulation of intracellular Ca 2+ signalling‐related process. Here, we have determined whether W‐7 would inhibit human ether gene (hERG or K v 11.1) potassium channels, hK v 1.5 channels or hK IR 2.1 channels expressed in human embryonic kidney (HEK) 293 cells. EXPERIMENTAL APPROACH The hERG channel current, hK v 1.5 channel current or hK IR 2.1 channel current was recorded with a whole‐cell patch clamp technique. KEY RESULTS It was found that the calmodulin inhibitor W‐7 blocked hERG, hK v 1.5 and hK IR 2.1 channels. W‐7 decreased the hERG current ( I hERG ) in a concentration‐dependent manner (IC 50 : 3.5 µM), and the inhibition was more significant at depolarization potentials between +10 and +60 mV. The hERG mutations in the S6 region Y652A and F656V , and in the pore helix S631A , had the IC 50 s of 5.5, 9.8 and 25.4 µM respectively. In addition, the compound inhibited hK v 1.5 and hK IR 2.1 channels with IC 50 s of 6.5 and 13.4 µM respectively. CONCLUSION AND IMPLICATIONS These results indicate that the calmodulin inhibitor W‐7 exerts a direct channel‐blocking effect on hERG, hK v 1.5 and hK IR 2.1 channels stably expressed in HEK 293 cells. Caution should be taken in the interpretation of calmodulin regulation of ion channels with W‐7.