title: Alterations of contractions and L-type Ca2+ currents by murrayafoline-A in rat ventricular myocytes.
abstract: We examined the effects of murrayafoline-A (1-methoxy-3-methylcarbazole, Mu-A), which is isolated from the dried roots of Glycosmis stenocarpa, on cell shortenings and L-type Ca2+ currents (ICa,L) in rat ventricular myocytes. Cell shortenings and ICa,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 ~20 μM. The maximal effect of Mu-A, approximately 175% of the control, was observed at ≥100 μM. The positive inotropic effect of Mu-A (25 μM) reached a maximum after ~2-min exposures, and then decayed after a ~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-induced positive inotropy, the ICa,L was assessed. Mu-A transiently enhanced the ICa,L. Concentration-dependence of the increase in ICa,L by Mu-A was similar to that of positive inotropic effect of Mu-A. The maximal effect of Mu-A (25 μM) on ICa,L was observed at 2-3 min after the application of Mu-A. A partial inhibition of ICa,L using verapamil (1 μM) 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.
authors.affiliation: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, South Korea; Department of Physics, SungKyunKwan University, Suwon, South Korea.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Son
authors.affiliation: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, South Korea.
authors.forename: Bojjibabu
authors.initials: B
authors.lastname: Chidipi
authors.affiliation: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, South Korea.
authors.forename: Joon-Chul
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Bioactive Products, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Rd., Hanoi, Vietnam.
authors.forename: Tran Thu
authors.initials: TT
authors.lastname: Huong
authors.affiliation: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, South Korea.
authors.forename: Bui Huu
authors.initials: BH
authors.lastname: Tai
authors.affiliation: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, South Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Physics, SungKyunKwan University, Suwon, South Korea.
authors.forename: Joung Real
authors.initials: JR
authors.lastname: Ahn
authors.affiliation: Department of Bioactive Products, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Rd., Hanoi, Vietnam.
authors.forename: Nguyen Manh
authors.initials: NM
authors.lastname: Cuong
authors.affiliation: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, South Korea. Electronic address: shwoo@cnu.ac.kr.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Woo
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018517:Plant Roots; D017207:Rats, Sprague-Dawley; D027821:Rutaceae; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D002316:Cardiotonic Agents; C443728:murrayafoline A; D014700:Verapamil
keywords: L-type Ca(2+) current; Murrayafoline-A (PubChem CID: 375150); Positive inotropy; Ventricular myocytes