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

Br J Pharmacol. 2010 Oct;161(4):872-84. doi: 10.1111/j.1476-5381.2010.00916.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Cell Line
  • Dose-Response Relationship, Drug
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
  • Ether-A-Go-Go Potassium Channels / genetics
  • Humans
  • Inhibitory Concentration 50
  • Kidney / cytology
  • Kv1.5 Potassium Channel / antagonists & inhibitors*
  • Mutation
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / administration & dosage
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Inwardly Rectifying / antagonists & inhibitors*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*


  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • KCNJ2 protein, human
  • Kv1.5 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels, Inwardly Rectifying
  • Sulfonamides
  • W 7
  • Calcium-Calmodulin-Dependent Protein Kinases