US EPA

1490130 

Journal Article 

The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide directly blocks human ether a-go-go-related gene potassium channels stably expressed in human embryonic kidney 293 cells 

Zhang, X; Jin, M; Sun, H; Zhang, S; Li, G 

2010 

Yes 

British Journal of Pharmacology
ISSN: 0007-1188
EISSN: 1476-5381 

161 

4 

872-884 

English 

20860665 

10.1111/j.1476-5381.2010.00916.x 

WOS:000282179000012 

https://www.scopus.com/inward/record.uri?eid=2-s2.0-77957222441&doi=10.1111%2fj.1476-5381.2010.00916.x&partnerID=40&md5=c771beb529fbebed7b149871c515255d
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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 a-go-go-related 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 mu M), 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 mu M 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 mu M 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. 

W-7; hERG channel; hK(v)1.5; hK(IR)2.1