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

BACKGROUND AND PURPOSEN‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalene sulphonamide (W‐7) is a well‐known calmodulin inhibitor used to study calmodulin regulation of intracellular Ca²⁺ 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 (IC₅₀: 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 IC₅₀s of 5.5, 9.8 and 25.4 µM respectively. In addition, the compound inhibited hK_v1.5 and hK_IR2.1 channels with IC₅₀s 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.

DOI: 10.1111/j.1476-5381.2010.00916.x

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