YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effects of Chrysosplenol C on Intracellular $Ca^{2+}$ Transient in Isolated Rat Ventricular Myocytes

Chrysosplenol C가 분리한 백서 심실 근세포 $Ca^{2+}$ Transient에 미치는 효과

  • Jung, Suk-Han (College of Pharmacy, IDRD, Chungnam National University) ;
  • Huong, Do Thi Thu (Institute of Chemistry, Vietnam Academy of Science and Technology (VAST)) ;
  • Sung, Tran Van (Institute of Chemistry, Vietnam Academy of Science and Technology (VAST)) ;
  • Cuong, Nguyen Manh (Department of Bioactive Products, Institute of Chemistry, VAST) ;
  • Kim, Young-Ho (College of Pharmacy, IDRD, Chungnam National University) ;
  • Woo, Sun-Hee (College of Pharmacy, IDRD, Chungnam National University)
  • 정석한 (충남대학교 약학대학, 의약품개발연구소) ;
  • 두 디 두 후옹 (베트남과학기술원 화학연구소) ;
  • 트란 반 성 (베트남과학기술원 화학연구소) ;
  • 뉘엔 만 콩 (베트남과학기술원 천연물화학연구소) ;
  • 김영호 (충남대학교 약학대학, 의약품개발연구소) ;
  • 우선희 (충남대학교 약학대학, 의약품개발연구소)
  • Received : 2011.03.23
  • Accepted : 2011.04.11
  • Published : 2011.04.30
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Abstract

Chrysosplenol C [5,6-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxychromen-4-one] is a flavonoid found in Miliusa balansae and Pterocaulon sphacelatum. We have recently shown that chrysosplenol C has positive inotropic effect in isolated rat ventricular myocytes. In the present study, we explored a possible mechanism for the positive inotropic effect of chrysosplenol C by examining intracellular $Ca^{2+}$ transients during action potentials. The intracellular $Ca^{2+}$ transients were measured by confocal $Ca^{2+}$ imaging in field-stimulated single rat ventricular myocytes. Chrysosplenol C (50 ${\mu}M$) significantly increased the magnitudes (${\Delta}F/F_0$) of $Ca^{2+}$ transients (control, $1.08{\pm}0.05$; chrysosplenol C, $1.25{\pm}0.03$; n=8, P<0.01). Half decay time of the action potential-induced $Ca^{2+}$ transient was not altered by chrysosplenol C (50 ${\mu}M$) (control, $154{\pm}6$ ms; chrysosplenol C, $167{\pm}11$ ms; n=21). The $Ca^{2+}$ content in the sarcoplasmic reticulum (SR), measured as caffeine (10 mM)-induced $Ca^{2+}$ transient, was significantly decreased by chrysosplenol C (50 ${\mu}M$). These results indicate that chrysosplenol C increases $Ca^{2+}$ transients without altering $Ca^{2+}$ removal kinetics in ventricular myocytes, providing a possible mechanism for its positive inotropic effect.

Keywords

References

  1. Huong, D. T., Kamperdick, C. and Sung, T. V. : Homogentisic acid derivatives from Miliusa balansae. J. Nat. Prod. 67, 445 (2004). https://doi.org/10.1021/np030195z
  2. Semple, S. J., Nobbs, S. F., Pyke, S. M., Reynolds, G. D. and Flower, R. L. : Antiviral flavonoid from Pterocaulon sphacelatum, an Australian Aboriginal medicine. J. Ethnoparmacol. 68, 283 (1999). https://doi.org/10.1016/S0378-8741(99)00050-1
  3. Tsuchiya, Y., Shimizu, M., Hiyama, Y., Otoh, K., Hashimoto, Y., Nakayama, M., Horie, T. and Morita, N. : Antiviral activity of natural occurring flavonoids in vitro. Chem. Pharm. Bull. 33, 3881 (1985). https://doi.org/10.1248/cpb.33.3881
  4. Huong, D. T., Luong, D. T., Thao, T. T. and Sung, T. V. : A new flavone and cytotoxic activity of flavonoid constituents isolated from Miliusa balansae (Annonaceae). Pharmazie. 60, 627 (2005).
  5. Son, M. J., Kim, H. K., Huong, D. T., Kim, Y. H., Sung, T. V., Cuong, N. M. and Woo, S. H. : Chrysosplenol C increases contraction in rat ventricular myocytes. J. Cardiovasc. Pharmacol. 57(2), 269 (2011).
  6. Verheijick, E. E., Wilders, R., Joyner, R. W., Golod, D. A., Kumar, R., Jongsma, H. J., Bouman, L. N. and van Ginneken, A. C. : Pacemaker synchronization of electrically coupled rabbit sinoatrial node cells. J. Gen. Physiol. 111, 95 (1998). https://doi.org/10.1085/jgp.111.1.95
  7. Kim, J. C., Son, M. J., Subedi, K. P., Li, Y., Ahn, J. R. and Woo, S. H. : Atrial Local $Ca^{2+}$ signaling and inositol 1,4,5- triphosphate receptors. Prog. Biophys. Mol. Biol. 103, 59 (2010). https://doi.org/10.1016/j.pbiomolbio.2010.02.002
  8. Adachi-Akahane, S., Cleemann, L. and Morad, M. : Crosssignaling between L-type $Ca^{2+}$ channels and ryanodine receptors in rat ventricular myocytes. J. Gen. Physiol. 108, 435 (1996). https://doi.org/10.1085/jgp.108.5.435
  9. Woo, S. H., Soldatov, N. M. and Morad, M. : Modulation of $Ca^{2+}$ signaling in rat atrial myocytes : possible role of the alpha1C carboxyl terminal. J. Physiol. 552, 437 (2003). https://doi.org/10.1113/jphysiol.2003.048330
  10. Sham, J. S., Hatem, S. N. and Morad, M. : Functional coupling of $Ca^{2+}$ channels and ryanodine receptors in cardiac myocytes. Proc. Natl. Acad. Sci. U.S.A. 92, 121 (1995). https://doi.org/10.1073/pnas.92.1.121
  11. Woo, S. H., Cleemann, L. and Morad, M. : $Ca^{2+}$ current-gated focal and local $Ca^{2+}$ release in rat atrial myocytes : evidence from rapid 2-D confocal imaging. J. Physiol. 543, 439 (2002). https://doi.org/10.1113/jphysiol.2002.024190
  12. Nbauer, M., Callewaert, G., Cleemann, L. and Morad, M. : Regulation of calcium release is gated by calcium current, not gating charge, in cardiac myocytes. Science 244, 800 (1989). https://doi.org/10.1126/science.2543067
  13. Fabiato, A. : Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac purkinje cell. J. Gen. Physiol. 85, 247 (1985). https://doi.org/10.1085/jgp.85.2.247
  14. Sandow, A. : Excitation-contraction coupling in muscular response. Yale J. Biol. Med. 25, 176 (1952).
  15. Bassani, R. A., Bassani, J. W. and Bers, D. M. : Mitochondrial and sarcolemmal $Ca^{2+}$ transport reduce $[Ca^{2+}]_{i}$ during caffeine contractures in rabbit cardiac myocytes. J. Physiol. 453, 591 (1992). https://doi.org/10.1113/jphysiol.1992.sp019246
  16. Guo, A. and Yang, H.T. : $Ca^{2+}$ removal mechanisms in mouse embryonic stem cell-derived cardiomyocytes. Am. J. Physiol. Cell. Physiol. 297, C732 (2009). https://doi.org/10.1152/ajpcell.00025.2009
  17. Endoh, M. : Force-frequency relationship in intact mammalian ventricular myocardium: physiological and pathological relevance. Eur. J. Pharmacol. 500, 73 (2004). https://doi.org/10.1016/j.ejphar.2004.07.013
  18. Endoh, M. : Signal transduction and $Ca^{2+}$ signaling in intact myocardium. J. Pharmacol. Sci. 100, 525 (2006). https://doi.org/10.1254/jphs.CPJ06009X
  19. Woo, S. H., Cleemann, L. and Morad, M. : Diversity of atrial local $Ca^{2+}$ signalling : evidence from 2-D confocal imaging in $Ca^{2+}$ buffered rat atrial myocytes. J. Physiol. 567, 905 (2005). https://doi.org/10.1113/jphysiol.2005.092270