CAJ | 학술논문

目的探讨ATP敏感性钾通道(KATP)激动剂Cromakaliam(CRK)对离体豚鼠心室肌细胞瞬间内向电流(Transient Inward Current,Iti)的作用,Iti和KATP在特发性室性心动过速中的作用机制.方法采用全细胞膜片钳及玻璃微电极记录方法,分别记录对照组、哇巴因组、CRK组、哇巴因加CRK组及哇巴因加CRK加格列本脲组对豚鼠乳头肌动作电位及心室肌细胞Iti和KATP电流的影响.结果 (1)哇巴因0.5umol/L灌流豚鼠心室乳头肌使动作电位延长,以动作电位复极20%、50%及90%的动作电位时程为著,可诱发延迟后除极(DAD)及触发激动(TA).还可以诱发Iti(126.9±10.8)pA,滞后时间为(1173.0±70.9)瑚,与对照组相比有统计学意义(P<0.01).(2)CRK 10 p,mol/L灌流心室乳头肌后可以缩短APD,使DAD幅度降低,偶联间期延长.CRK可以有效的抑制Iti.(3)CRK 50umol/L灌流豚鼠心室肌细胞后,KATP电流高至(342±89)pA,与对照组相比差异有统计学意义(P<0.01).ATP敏感性钾通道阻滞剂格列本脲10umol/L灌流豚鼠心室肌细胞,可拮抗CRK对APD和离子流的作用.结论 CRK可以减弱哇巴因对心肌细胞的毒性作用,使APD缩短,中止DAD及触发激动对心肌细胞具有保护作用.CRK的作用与抑制Iti电流、增加KATP电流有关.
목적 탐토ATP민감성갑통도(KATP)격동제Cromakaliam(CRK)대리체돈서심실기세포순간내향전류(Transient Inward Current,Iti)적작용,Iti화KATP재특발성실성심동과속중적작용궤제.방법 채용전세포막편겸급파리미전겁기록방법,분별기록대조조、왜파인조、CRK조、왜파인가CRK조급왜파인가CRK가격렬본뇨조대돈서유두기동작전위급심실기세포Iti화KATP전류적영향.결과 (1)왜파인0.5umol/L관류돈서심실유두기사동작전위연장,이동작전위복겁20%、50%급90%적동작전위시정위저,가유발연지후제겁(DAD)급촉발격동(TA).환가이유발Iti(126.9±10.8)pA,체후시간위(1173.0±70.9)호,여대조조상비유통계학의의(P<0.01).(2)CRK 10 p,mol/L관류심실유두기후가이축단APD,사DAD폭도강저,우련간기연장.CRK가이유효적억제Iti.(3)CRK 50umol/L관류돈서심실기세포후,KATP전류고지(342±89)pA,여대조조상비차이유통계학의의(P<0.01).ATP민감성갑통도조체제격렬본뇨10umol/L관류돈서심실기세포,가길항CRK대APD화리자류적작용.결론 CRK가이감약왜파인대심기세포적독성작용,사APD축단,중지DAD급촉발격동대심기세포구유보호작용.CRK적작용여억제Iti전류、증가KATP전류유관.
Objective To investigate the mechanism of ATP-sensitive potassium channel(KATP) activator cromakaliam(CRK)on action potentials and transient inward current(Iti)in isolated guinea pig papillary and ventricular myocytes and to explore the mechanisms of effects of Iti and KATP treatment in idiopathic ventricular tachycardia.Methods The whole-cell patch clamp recording technique was used to detect the action potentials and Iti and KATP current alterations during the stimulated and triggered activity. Myocytes were isolated from guinea pig ventricle by enzyme digestion.The experiment was divided into four groups:(1)Control;(2)Control+Ouabain;(3)Control+CRK;(4)Control+Ouabain+CRK.(5) Control+Ouabain+CRK+glibenclamide(GLB).The action potential of guinea pig papillary muscules was measured by using standard microelectrode.The parameters in the experimant incluced the amplitude (APA),resting potentials(RP),action potentials duration(APD),as well as maximum rise of the action potential(Vmax).Results (1)When the guinea pig ventricular papillary myocytes were pretreated with Ouabain 0.5~mol/L,APD prolonged significantly,especially APD20,APD50,APD90.Delayed after depotorazion(DAD)and triggered activity were elicited.Iti currents and DAD as well as triggered activity increased.Iti current was(126.9±10.8)pA,lagT(1173.0±70.9)ms(n=10,P<0.01).(2)When guinea pig ventricular myocytes were pretreated with CRK(10 umol/L),APD was shortened and the amplitude of DAD was lowered.The coupling time in CRK group was significantly prolonged compared with Ouabain group(n=10,P<0.01).(3)CRK 50umol/L pretreatment of the ventricular myocytes led to an increase of KATP up to(342±89)pA,which was statistically significant as compared with the control group(P<0.01).ATP-sensitive potassium channel blocker glibeclamide(10umol/L)could antagonize the effects of CRK on APD and Iti currents.Conciusion CRK might reduce the toxic effect of Ouabain on cardiomyocytes,shorten APD,terminate DAD and trigger excitation,and have protective effect on cardiomyocytes.The effects of CRK,may be associated with the inhibiting Iti current and increasing KATP.