Imipramine blocks the transient outward potassium current in rat ventricular myocytes

目的：研究丙咪嗪对大鼠心室细胞瞬间外向钾电流（Ｉｔｏ）的抑制作用．方法：膜片箝全细胞记录法．结果：丙咪嗪对Ｉｔｏ有浓度依赖性抑制作用，ＩＣ５０为６０μｍｏｌ·Ｌ－１，并明显加速该电流的灭活时程．在不同的测试电位下，丙咪嗪对该电流的抑制百分率没有差别．丙咪嗪对Ｉｔｏ的稳态激活和灭活曲线的半数膜电位都无明显影响，对Ｉｔｏ灭活后的再复活时程有延长趋势，但不显著（τｃｏｎｔｒｏｌ＝３７±１１ｍｓ，τｄｒｕｇ＝５８±１７ｍｓ，Ｐ＞００５），但可明显加速条件刺激时程对Ｉｔｏ的灭活（τｃｏｎｔｒｏｌ＝２２±８ｍｓ，τｄｒｕｇ＝１４±５ｍｓ，Ｐ＜００５）．结论：丙咪嗪对大鼠心室细胞瞬间外向钾电流有浓度依赖性和电压非依赖性抑制作用，作用特点属于开放通道阻断．

IM: To examine the effects of imipramine on transient outward potassium current ( I to ) in rat ventricular myocytes. METHODS: The patch clamp whole cell recording techniques were used. RESULTS: Imipramine resulted in a concentration dependent inhibition of I to with the IC 50 of 6 0 μmol·L -1 and a concentration dependent accelera￣tion of I to inactivation. The blocking showed no difference at different testing membrane potentials. Imipramine produced slight effects (about 3 and 4 mV, respectively) on steady state activation and inactivation curves of I to , and tended to prolong the recovery of I to from inactivation (τ control =37±11 ms; τ drug =58±17 ms), but not significant ( n =4, P >0 05). The inhibitory effect of imipramine on I to was increased when the prepulses were prolonged progressively from 0 to 120 ms. (τ control =22±8 ms; τ drug =14±5 ms). CONCLUSIONS: Imipramine blocked I to in concentration dependent but voltage independent manners, and with “open channel blocking” properties.