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 1.48μM. 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±0.01μM(-1)s(-1) and 2.59±0.14s(-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 2Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10μM), 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.
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 1.48μM. 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±0.01μM(-1)s(-1) and 2.59±0.14s(-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 2Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10μM), 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.
Authors: Han Sol Kim; Hongliang Li; Hye Won Kim; Sung Eun Shin; Il-Whan Choi; Amy L Firth; Hyoweon Bang; Young Min Bae; Won Sun Park Journal: J Biosci Date: 2016-12 Impact factor: 1.826
Authors: Hongliang Li; Han Sol Kim; Hye Won Kim; Sung Eun Shin; Won-Kyo Jung; Kwon-Soo Ha; Eun-Taek Han; Seok-Ho Hong; Amy L Firth; Young Min Bae; Il-Whan Choi; Won Sun Park Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2016-03-31 Impact factor: 3.000