Alterations of contractions and L-type Ca2+ currents by murrayafoline-A in rat ventricular myocytes

作者:Son Min Jeong; Chidipi Bojjibabu; Kim Joon Chul; Tran Thu Huong; Tai Bui Huu; Kim Young Ho; Ahn Joung Real; Nguyen Manh Cuong; Woo Sun Hee*
来源:European Journal of Pharmacology, 2014, 740: 81-87.
DOI:10.1016/j.ejphar.2014.07.001

摘要

We examined the effects of murrayafoline-A (1-methoxy-3-methylcarbazole, Mu-A), which is isolated from the dried roots of Glycosniis steriocarpn, on cell shortenings and L-type Ca2+ currents (I-Ca,I-L) in rat ventricular myocytes. Cell shortenings and I-Ca,I-L were measured using the video edge detection method and patch clamp techniques, respectively. Mu-A transiently increased cell shortenings in a concentration dependent manner with an EC50 of similar to 20 mu M. The maximal effect of Mu-A, approximately 175% of the control, was observed at %26gt;= 100 mu M The positive inotropic effect of Mu-A (25 mu M) reached a maximum after similar to 2-min exposures, and then decayed after a similar to 1-min steady-state. During the Mu-A-induced positive inotropy, the rate of contraction was accelerated, whereas the rate of relaxation was not significantly altered. To understand the possible mechanism for the Mu-A-inducecl positive inotropy, the I-Ca,I-L was assessed. Mu-A transiently enhanced the I-Ca,I-L. Concentration-dependence of the increase in I-Ca,I-L by Mu-A was similar to that of positive inotropic effect of Mu-A. The maximal effect of Mu-A (25 mu M) on I-Ca,I-L was observed at 2-3 min after the application of Mu-A. A partial inhibition of I-Ca,I-L using verapamil (1 mu M) induced a right shift of concentration-response curve of the positive inotropic effect of Mu-A and significantly attenuated the effect. These results suggest that Mu-A may transiently enhance contractility, at least in part, by increasing the Ca2+ influx through the L-type Ca2+ channels in rat ventricular myocytes.

  • 出版日期2014-10-5