The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells |
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Authors: | Da Hye Hong Il-Whan Choi Youn Kyoung Son Dae-Joong Kim Sung Hun Na Won-Kyo Jung Young Wook Yoon Won Sun Park |
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Institution: | 1. Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea;2. Department of Microbiology, Inje University College of Medicine, Busan, 614-735, South Korea;3. Department of Anatomy and Cell Biology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea;4. Institute of Medical Sciences, Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea;5. Department of Marine Life Science, Chosun University, Gwangju 501-759, South Korea;6. Department of Physiology, Korea University College of Medicine, Seoul, 136-705, South Korea |
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Abstract: | AimsWe examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K+ (Kv) channels.Main methodsElectrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells.Key findingsThe 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.SignificanceBased on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition. |
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