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1、从兴奋收缩耦联机制看心力衰竭 正性肌力药物发展田野教授哈医大二院心内科提要兴奋-收缩耦联机制正性肌力药的循证研究洋地黄制剂β-肾上腺素能受体激动剂磷酸二酯酶抑制剂钙增敏剂新型正性肌力药的探索亚硝酰氢兴奋-收缩耦联机制Excitation-contraction(EC)couplingisatermcoinedin1952todescribethephysiologicalprocessofconvertinganelectricalstimulustomechanicalresponse.SandowA(1952).
2、"Excitation-contractioncouplinginmuscularresponse.".YaleJBiolMed25(3):176–201.PMID130159500Excitation-contractioncouplingCardiacexcitation–contractioncouplingistheprocessfromelectricalexcitationofthemyocytetocontractionoftheheart(whichpropelsbloodout).Theubiqui
3、toussecondmessengerCa2+isessentialincardiacelectricalactivityandisthedirectactivatorofthemyofilaments,whichcausecontraction.Bers,D.M.Excitation–ContractionCouplingandCardiacContractileForceedn2(KluwerAcademic,Dordrecht,Netherlands,2001).Cardiacexcitation–contra
4、ctioncouplingCardiactissue(Guinea-pigventricularcell)CardiactissueCardiaccellsTheactionpotentialmovesthroughsarcolemmaTtubeCa2+-inducedCa2+-releaseCa++Ca++Ca++Ca2+PlbCa2+Ca++Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca++Ca++Ca++Ca++Ca2+Ca++Ca++Ca++Ca++Ca2+Ca++Ca++Ca2+Ca++Ca+
5、+Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca2+Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Na+Na+Na+Ca2+SERCASRRyRL-TypeCa2+ChannelNa+/Ca2+ExchangerCa++SarcolemmaCa2+ActinTropomyosinTroponinTitinMyosinMyosin-binding-proteinCCapZTropomodulinCross-l
6、inkingprotein肌联蛋白（Titin）将粗肌丝与Z-线连接，维持肌原纤维的完整性和稳定性，保持舒张肌肉的静息张力，使粗肌丝处于肌小节的中央位置，使受牵拉的肌肉可恢复初始状态，以保证肌肉收缩时张力的输出。ZZTitin28,000aminoacids(3MDa)thelargestproteinknowninmammals.TitinThemolecularbasisformyocardialcontractionThinfilament(Actin,Tropom-yosin,Troponin)Thickfi
7、lament(Myosin)OtherproteinsChien,K.R.,1999F-actinZ-lineZ-lineThinFilamentProteinsGtoFactinMW42kDaTheblueandgreymoleculesareactinmonomers(MW42.000)KenC.Holmes:Max-Planck-InstituteG-ActinF-Actin肌动蛋白以两种形式存在,即单体和多聚体。单体的肌动蛋白是由一条多肽链构成的球形分子,又称球状肌动蛋白(globularactin,G-ac
8、tin),外形类似花生果。肌动蛋白的多聚体形成肌动蛋白丝,称为纤维状肌动蛋白(fibrosactin,F-actin)。在电子显微镜下,F-肌动蛋白呈双股螺旋状,直径为8nm,螺旋间的距离为37nm。LorenzmodelofF-actin.AsingleG-actinmonomerwithinter-actincontactsurfacesi
