Murrayafoline-A에 의한 심실 근육세포 Ca2+

Enhancement of Ca 2+ in Rat Ventricular Myocytes

Murrayafoline-A (1-methoxy-3-methylcarbazole) is a monomeric carbazole alkaloid found in Murraya euchres- tifolia HAYATA and Glycosmis stenocarpa. We have recently shown that murrayafoline-A has positive inotropic effect in iso-lated rat ventricular myocytes. To know possible mechanisms for the positive inotropic effect of murrayafoline-A we examined the effects of murrayafoline-A on in situ behavior of cardiac Ca 2+ release units (‘Ca2+ sparks’) and sarcoplasmic reticulum (SR) Ca 2+ loading using confocal Ca 2+ imaging method in single rat ventricular myocytes. Murrayafoline-A sig-nificantly increased the frequency (events/(103μm2· s)) of Ca 2+sparks in a concentration-ndent manner, with an EC50 of 28±6.4 μM and a maximal ~twofold change. The Ca 2+ content in the SR, measured as caffeine (10 mM)-induced Ca 2+transient, was significantly increased by murrayafoline-A (≈116% and ≈123% of control at 25 and 100 μM, respectively). In addition, murrayafoline-A significantly increased the fractional Ca 2+ release, suggesting increase in the efficacy of Ca 2+ release at given SR Ca 2+ loading. These results suggest that murrayafoline-A may enhance contractility via increase in Ca 2+ release from the SR through the ryanodine receptors in ventricular myocytes.