The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K + channels in rabbit coronary arterial smooth muscle cells

Da Hye Hong, Il Whan Choi, Youn Kyoung Son, Dae Joong Kim, Sung Hun Na, Won Kyo Jung, Young Wook Yoon, Won Sun Park

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Aims We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K+ (Kv) channels. Main methods Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells. Key findings The Kv current amplitude was inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48 μM. Without alteration of the kinetics of activation, LY294002 accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for LY294002 were 1.83 ± 0.01 μM - 1 s- 1 and 2.59 ± 0.14 s- 1, respectively. Application of LY294002 had no significant impact on the steady-state activation or inactivation curves. In the presence of LY294002, the recovery time constant from inactivation was increased, and Kv channel inhibition increased under train pulses (1 or 2 Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10 μM), did not affect the Kv current, and did not change the inhibitory effect of LY294002. Significance Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.

Original languageEnglish
Pages (from-to)916-922
Number of pages7
JournalLife Sciences
Volume92
Issue number17-19
DOIs
Publication statusPublished - 2013 May 20

Fingerprint

Phosphatidylinositol 3-Kinase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphatidylinositol 3-Kinases
Smooth Muscle Myocytes
Muscle
Cells
Rabbits
Electric potential
Chemical activation
Rate constants
Association reactions
Recovery
Kinetics

Keywords

  • Coronary artery
  • K channel
  • LY294002
  • Voltage-dependent

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hong, D. H., Choi, I. W., Son, Y. K., Kim, D. J., Na, S. H., Jung, W. K., ... Park, W. S. (2013). The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K + channels in rabbit coronary arterial smooth muscle cells. Life Sciences, 92(17-19), 916-922. https://doi.org/10.1016/j.lfs.2013.03.006

The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K + channels in rabbit coronary arterial smooth muscle cells. / Hong, Da Hye; Choi, Il Whan; Son, Youn Kyoung; Kim, Dae Joong; Na, Sung Hun; Jung, Won Kyo; Yoon, Young Wook; Park, Won Sun.

In: Life Sciences, Vol. 92, No. 17-19, 20.05.2013, p. 916-922.

Research output: Contribution to journalArticle

Hong, Da Hye ; Choi, Il Whan ; Son, Youn Kyoung ; Kim, Dae Joong ; Na, Sung Hun ; Jung, Won Kyo ; Yoon, Young Wook ; Park, Won Sun. / The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K + channels in rabbit coronary arterial smooth muscle cells. In: Life Sciences. 2013 ; Vol. 92, No. 17-19. pp. 916-922.
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AB - Aims We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K+ (Kv) channels. Main methods Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells. Key findings The Kv current amplitude was inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48 μM. Without alteration of the kinetics of activation, LY294002 accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for LY294002 were 1.83 ± 0.01 μM - 1 s- 1 and 2.59 ± 0.14 s- 1, respectively. Application of LY294002 had no significant impact on the steady-state activation or inactivation curves. In the presence of LY294002, the recovery time constant from inactivation was increased, and Kv channel inhibition increased under train pulses (1 or 2 Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10 μM), did not affect the Kv current, and did not change the inhibitory effect of LY294002. Significance Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.

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