The phosphoinositide 3-kinase inhibitor LY294002 enhances cardiac myocyte contractility via a direct inhibition of Ik,slow currents

Cardiovascular Research

Volumn 62, Issue 3, 2004, Pages 509-520

  Sun, Hui ^a   Oudit, Gavin Y ^a   Ramirez, Rafael J ^a   Costantini, Danny ^a   Backx, Peter H ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Action potential; Ca 2+ transient; Cardiac myocyte contractility; Ik,slow currents; LY294002; Phosphoinositide 3 kinase

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 4 AMINOPYRIDINE; CALCIUM; INWARDLY RECTIFYING POTASSIUM CHANNEL; TETRYLAMMONIUM; WORTMANNIN;

ANIMAL CELL; ARTICLE; CALCIUM CELL LEVEL; CALCIUM TRANSPORT; CELL ISOLATION; CONTROLLED STUDY; DRUG EFFECT; HEART DEPOLARIZATION; HEART LEFT VENTRICLE WALL; HEART MUSCLE CELL; HEART MUSCLE CONTRACTILITY; MALE; MOUSE; MUSCLE ACTION POTENTIAL; NONHUMAN; PATCH CLAMP; POTASSIUM CURRENT; PRIORITY JOURNAL; SARCOPLASMIC RETICULUM; VOLTAGE CLAMP;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ACTION POTENTIALS; ANDROSTADIENES; ANIMALS; CALCIUM; CELL SIZE; CHROMONES; DOSE-RESPONSE RELATIONSHIP, DRUG; INDOLES; MALE; MICE; MICE, INBRED C57BL; MICROSCOPY, FLUORESCENCE; MORPHOLINES; MYOCYTES, CARDIAC; PATCH-CLAMP TECHNIQUES; POTASSIUM CHANNELS, VOLTAGE-GATED; SARCOPLASMIC RETICULUM;

EID: 2442585130     PISSN: 00086363     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cardiores.2004.01.029     Document Type: Article

References (36)

1. Vanhaesebroeck B., Waterfield M.D. Signaling by distinct classes of phosphoinositide 3-kinases. Exp. Cell Res. 253:1999;239-254
2. Cantley L.C. The phosphoinositide 3-kinase pathway. Science. 296:2002;1655-1657
3. Stein R.C., Waterfield M.D. PI3-kinase inhibition: a target for drug development? Mol. Med. Today. 6:2000;347-357
4. Walker E.H., Pacold M.E., Perisic O., et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell. 6:2000;909-919
5. Jo S.H., Leblais V. Wang PH, et al. Phosphatidylinositol 3-kinase functionally compartmentalizes the concurrent G(s) signaling during beta2-adrenergic stimulation. Circ. Res. 91:2002;46-53
6. 2+-dependent positive inotropic effects in failing human myocardium. Circ. Res. 92:2003;169-176
7. Schluter K.D., Goldberg Y., Taimor G., et al. Role of phosphatidylinositol 3-kinase activation in the hypertrophic growth of adult ventricular cardiomyocytes. Cardiovasc. Res. 40:1998;174-181
8. Kodama H., Fukuda K., Pan J., et al. Significance of ERK cascade compared with JAK/STAT and PI3-K pathway in gp130-mediated cardiac hypertrophy. Am. J. Physiol. 279:2000;H1635-H1644
9. Aikawa R., Nawano M., Gu Y., et al. Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation. 102:2000;2873-2879
10. Tong H., Chen W., Steenbergen C., Murphy E. Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. Circ. Res. 87:2000;309-315
11. Ui M., Okada T., Hazeki K., Hazeki O. Wortmannin as a unique probe for an intracellular signalling protein, phosphoinositide 3-kinase. Trends Biochem. Sci. 20:1995;303-307
12. Yano H., Nakanishi S., Kimura K., et al. Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. J. Biol. Chem. 268:1993;25846-25856
13. Vlahos C.J., Matter W.F., Hui K.Y., Brown R.F. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 269:1994;5241-5248
14. Walker E.H., Perisic O., Ried C., et al. Structural insights into phosphoinositide 3-kinase catalysis and signalling. Nature. 402:1999;313-320
15. Crackower M.A., Oudit G.Y., Kozieradzki I., et al. Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Cell. 110:2002;737-749
16. Sah R., Ramirez R.J., Kaprielian R., Backx P.H. Alterations in action potential profile enhance excitation-contraction coupling in rat cardiac myocytes. J. Physiol. 533:2001;201-214
17. + currents in adult mouse ventricular myocytes. J. Gen. Physiol. 113:1999;661-678
18. Zhou J., Kodirov S., Murata M., et al. Regional upregulation of Kv2.1-encoded current, IK, slow2, in Kv1DN mice is abolished by crossbreeding with Kv2DN mice. Am. J. Physiol. 284:2003;H491-H500
19. Xu H., Barry D.M., Li H., et al. Attenuation of the slow component of delayed rectification, action potential prolongation, and triggered activity in mice expressing a dominant-negative Kv2 alpha subunit. Circ. Res. 85:1999;623-633
20. Straube S., Parekh A.B. Effects of phosphatidylinositol kinase inhibitors on the activation of the store-operated calcium current ICRAC in RBL-1 cells. Pflugers Arch. 442:2001;391-395
21. Ethier M.F., Madison J.M. LY294002, but not wortmannin, increases intracellular calcium and inhibits calcium transients in bovine and human airway smooth muscle cells. Cell Calcium. 32:2002;31-38
22. Warashina A. Mechanism by which wortmannin and LY294002 inhibit catecholamine secretion in the rat adrenal medullary cells. Cell Calcium. 29:2001;239-247
23. Stein R.C., Waterfield M.D. PI3-kinase inhibition: a target for drug development? Mol. Med. Today. 6:2000;347-357
24. London B., Jeron A., Zhou J., et al. Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel. Proc. Natl. Acad. Sci. U. S. A. 95:1998;2926-2931
25. (K, slow) and resistance to drug-induced qt prolongation. Circ. Res. 88:2001;940-946
26. El-Kholy W., Macdonald P.E., Lin J.H., et al. The phosphatidylinositol 3-kinase inhibitor LY294002 potently blocks K(V) currents via a direct mechanism. FASEB J. 17:2003;720-722
27. Ding J., Vlahos C.J., Liu R., et al. Antagonists of phosphatidylinositol 3-kinase block activation of several novel protein kinases in neutrophils. J. Biol. Chem. 270:1995;11684-11691
28. (K, slow). Am. J. Physiol. 281:2001;H1201-H1209
29. Armoundas A.A., Hobai I.A., Tomaselli G.F., et al. Role of sodium-calcium exchanger in modulating the action potential of ventricular myocytes from normal and failing hearts. Circ. Res. 93:2003;46-53
30. (to)). J. Physiol. 546:2003;5-18
31. + current modulates repolarization and excitation-contraction coupling in adult mouse ventricle. J. Physiol. 504:1997;557-563
32. Bers M.D. Excitation-Contraction Coupling and Cardiac Contractile Force. 2nd ed. 2001;133-155 Kluwer Academic Publishing, Dordrecht
33. Shannon T.R., Ginsburg K.S., Bers D.M. Potentiation of fractional sarcoplasmic reticulum calcium release by total and free intra-sarcoplasmic reticulum calcium concentration. J. Biophys. 78:2000;334-343
34. 2+ sensing sites. Biophys. J. 75:1998;2801-2810
35. Ghosh-Choudhury N., Abboud S.L., Chandrasekar B., Ghosh G. Choudhury, BMP-2 regulates cardiomyocyte contractility in a phosphatidylinositol 3 kinase-dependent manner. FEBS Lett. 544:2003;181-184
36. + channel diversity in the mammalian myocardium. J. Physiol. 525:2000;285-298