title: The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells.
abstract: OBJECTIVE
  We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K(+) (Kv) channels.
  
  
  METHODS
  Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea.
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Hong
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Dae-Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Na
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Yoon
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology*; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D024642:Potassium Channels, Voltage-Gated; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000077191:Wortmannin