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Enhancement of $Ca^{2+}$ Spark Occurrence by Murrayafoline-A in Rat Ventricular Myocytes  

Kim, Joon-Chul (College of Pharmacy, Chungnam National University)
Cuong, Nguyen Manh (Institute of Natural Products Chemistry, VAST)
Woo, Sun-Hee (College of Pharmacy, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.58, no.4, 2014 , pp. 245-249 More about this Journal
Abstract
Murrayafoline-A (1-methoxy-3-methylcarbazole) is a monomeric carbazole alkaloid found in Murraya euchrestifolia HAYATA and Glycosmis stenocarpa. We have recently shown that murrayafoline-A has positive inotropic effect in isolated 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 ('$Ca^{2+}$ sparks') and sarcoplasmic reticulum (SR) $Ca^{2+}$ loading using confocal $Ca^{2+}$ imaging method in single rat ventricular myocytes. Murrayafoline-A significantly increased the frequency (events/($10^3{\mu}m^2{\cdot}s$)) of $Ca^{2+}$ sparks in a concentration-dependent manner, with an $EC_{50}$ of $28{\pm}6.4{\mu}M$ 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 (${\approx}$116% and ${\approx}$123% of control at 25 and 100 ${\mu}M$, 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.
Keywords
murrayafoline-A; $Ca^{2+}$ spark; ventricular myocytes; SR $Ca^{2+}$ content; fractional $Ca^{2+}$ release;
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