- 作者: Ming-Jai Su wen-Pin Chen Tase-Yueh Lo tian-Shung Wu
- 作者服務機構: Department of Pharmacology, college of Medicine, National Taiwan University, Taipei, and Department of Chemistry, National Chen-Kong University, Tainan, Taiwan
- 中文摘要: --
- 英文摘要: We investigated the electrophysiological effect and anti-arrhythmic potential of cinnamophilin (Cinn), a throm-boxane A antagonist isolated from Cinnamomum phi-lippinense, on rat cardiac tissues. Action potential andionic currents in single rat ventricular cells were exam-ined by current clamp or voltage clamp in a whole-cellconfiguration. In 9 episodes of ischemia-reperfusion ar-rhythmia, 10 μM Cinn converted 6 of them to normal sin-us rhythm. Cinn suppressed the maximal rate of rise ofthe action potential upstroke (V ) and prolonged theaction potential duration at 50% repolarization (APD ).Voltage clamp study showed that the suppression ofV by Cinn was associated with an inhibition of sodiuminward current (I , IC =10.0±0.4μM). At 30μM, V for the steady-state inactivation curve of I was shiftedfrom -84.1±0.2 to -93.0±0.5 mV. Cinn also reducedcalcium inward current (IC ) dose-dependently with anIC value of 9.5±0.3 μM. Cinn(10 μM) reduced the l with a negative shift of V for the steady-state inactiva-tion curve of I from -32.2±0.3 to -50.7±0.4 mV. Theprolongation of APD was associated with an inhibitionof the integral of potassium outward current with IC50values between 4.8 and 7.1μM. At 10μM, Cinn reducedI without a negative shift of its voltage-dependentsteady-state inactivation curves. The inhibition of tran-sient outward current(I ) by Cinn (3-30μM) was associ-ated with an acceleration of its time constant of inactiva-tion and negative shift of its potential-dependent steady-state inactivation curves. The equilibrium dissociationconstant(K ) of Cinn to inhibit open state I channels, ascalculated from the time constant of developing block,was 18.3μM. The time constant of recovery of I frominactivation state was unaffected by Cinn. The rate con-stant for the relief from the depolarization-dependentblock of I was calculated to be 23.9 ms. As comparedwith its effect on I , Cinn exerted about half the potencyto block INa and I . These results indicate that the inhibi-tion of I , I and I may contribute to the antiarrhythmicactivity of Cinn against ischemia-reperfusion arrhyth-mia.
- 中文關鍵字: --
- 英文關鍵字: Cinnamophilin. Potassium current. Sodium current. Calcium current. Action potential. Reperfusion arrhythmia