CAJ | 학술논문

目的：探讨β1-肾上腺受体(β1-AR)激活对慢性心衰( CHF)豚鼠心室肌细胞快激活延迟整流钾电流( IKr )的影响及机制。方法制备豚鼠CHF模型,采用全细胞膜片钳技术记录心室肌细胞IKr ,观察选择性β1-AR激动剂对CHF心室肌细胞IKr的影响,并采用蛋白激酶A( PKA)及钙调蛋白激酶Ⅱ( CaMKⅡ)抑制剂干预研究其机制。结果β1-AR激动剂扎莫特罗使CHF心室肌细胞IKr减少了(52±8)%,延长动作电位时程。β1-AR阻滞剂CGP20712A完全抑制扎莫特罗对CHF心室肌细胞IKr的减弱作用。应用PKA抑制剂KT5720预处理,扎莫特罗仅使CHF心室肌细胞IKr减少了(28±3)%。应用CaMKⅡ抑制剂KN93预处理,KN93不能减弱扎莫特罗对CHF心室肌细胞IKr的抑制作用。结论β1-AR激活抑制 CHF 心室肌细胞 IKr；心衰时β1-AR 通过PKA通路抑制心室肌细胞IKr ,与CaMKⅡ通路无关。
목적：탐토β1-신상선수체(β1-AR)격활대만성심쇠( CHF)돈서심실기세포쾌격활연지정류갑전류( IKr )적영향급궤제。방법제비돈서CHF모형,채용전세포막편겸기술기록심실기세포IKr ,관찰선택성β1-AR격동제대CHF심실기세포IKr적영향,병채용단백격매A( PKA)급개조단백격매Ⅱ( CaMKⅡ)억제제간예연구기궤제。결과β1-AR격동제찰막특라사CHF심실기세포IKr감소료(52±8)%,연장동작전위시정。β1-AR조체제CGP20712A완전억제찰막특라대CHF심실기세포IKr적감약작용。응용PKA억제제KT5720예처리,찰막특라부사CHF심실기세포IKr감소료(28±3)%。응용CaMKⅡ억제제KN93예처리,KN93불능감약찰막특라대CHF심실기세포IKr적억제작용。결론β1-AR격활억제 CHF 심실기세포 IKr；심쇠시β1-AR 통과PKA통로억제심실기세포IKr ,여CaMKⅡ통로무관。
Aim To investigate the effects of β1-ad-renergic receptor (β1-AR ) on rapid component of the delayed rectifier potassium current ( IKr ) in ventricular <br> myocytes of guinea pigs with chronic heart failure ( CHF) . Methods The CHF model of guinea pigs was established by descending thoracic aortic banding . <br> Whole-cell patch-clamp technique was used to record IKr in ventricular myocytes. The effects ofβ1-AR on IKr in CHF ventricular myocytes were detected and its mechanisms were studied by pretreatment with protein kinase A ( PKA ) inhibitor and calmodulin kinase II( CaMK II) inhibitor. Results In CHF ventricular myocytes, xamoterol, the selectiveβ1-AR agonist, de-creased IKr by (52±8)% and prolonged action poten-tial duration. These effects were completely abolished by pretreatment of myocytes with CGP20712A, a selec-tive β1-AR antagonist. íamoterol only decreased IKr <br> by (28±3)% by pretreatment of CHF myocytes with specific PKA inhibitor KT5720 . KN93 , an inhibitor of CaMKII, did not attenuate the inhibitory effect on CHF ventricular myocytes. Conclusion IKr is inhibi-ted by β1-AR activation in CHF ventricular myocytes. PKA, but not CaMKII signaling pathway is involved in, at least in part, the inhibitory effect ofβ1-AR acti-vation on IKr.