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

Abstract

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 v11.1) potassium channels, hK v1.5 channels or hK IR2.1 channels expressed in human embryonic kidney (HEK) 293 cells. EXPERIMENTAL APPROACH The hERG channel current, hK v1.5 channel current or hK IR2.1 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 v1.5 and hK IR2.1 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 50s of 5.5, 9.8 and 25.4 μM respectively. In addition, the compound inhibited hK v1.5 and hK IR2.1 channels with IC 50s 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 v1.5 and hK IR2.1 channels stably expressed in HEK 293 cells. Caution should be taken in the interpretation of calmodulin regulation of ion channels with W-7. © 2010 The British Pharmacological Society.