The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

Toxicology and Applied Pharmacology
Hongliang LiWon Sun Park

Abstract

We investigated the effects of the calmodulin inhibitor CGS 9343B on voltage-dependent K(+) (Kv) channels using whole-cell patch clamp technique in freshly isolated rabbit coronary arterial smooth muscle cells. CGS 9343B inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 0.81μM. The decay rate of Kv channel inactivation was accelerated by CGS 9343B. The rate constants of association and dissociation for CGS 9343B were 2.77±0.04μM(-1)s(-1) and 2.55±1.50s(-1), respectively. CGS 9343B did not affect the steady-state activation curve, but shifted the inactivation curve toward to a more negative potential. Train pulses (1 or 2Hz) application progressively increased the CGS 9343B-induced Kv channel inhibition. In addition, the inactivation recovery time constant was increased in the presence of CGS 9343B, suggesting that CGS 9343B-induced inhibition of Kv channel was use-dependent. Another calmodulin inhibitor, W-13, did not affect Kv currents, and did not change the inhibitory effect of CGS 9343B on Kv current. Our results demonstrated that CGS 9343B inhibited Kv currents in a state-, time-, and use-dependent manner, independent of calmodulin inhibition.

References

Jul 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·H HidakaT Nagata
Jan 1, 1980·British Journal of Pharmacology·Y HaraH Kuriyama
Aug 1, 1996·Current Opinion in Cell Biology·F Striggow, B E Ehrlich
Jan 15, 1999·Acta Physiologica Scandinavica·N B Standen, J M Quayle
Feb 4, 2006·Biochemical and Biophysical Research Communications·Youn Kyoung SonJin Han
Oct 20, 2009·Progress in Biophysics and Molecular Biology·Eun A KoJin Han
Nov 14, 2012·Biochemical and Biophysical Research Communications·Da Hye HongWon Sun Park
Nov 6, 2013·Biochimica Et Biophysica Acta·Martin W Berchtold, Antonio Villalobo
May 28, 2014·The Journal of General Physiology·Manu Ben-Johny, David T Yue

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Citations

Jul 23, 2019·Clinical and Experimental Pharmacology & Physiology·Hongliang LiWon Sun Park

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