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 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

resultsIt 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.