Modulation of cardiac inward rectifier K(+)current by halothane and isoflurane.
Modulation of cardiac inward rectifier K(+)current by halothane and isoflurane.
复制标题
氟烷和异氟烷对心脏内向整流 K( ) 电流的调节。
DOI：
10.1097/00000539-200004000-00010
复制
发表时间：
2000
影响因子：
5.7
通讯作者：
Kwok,WM
中科院分区：
文献类型：
--
作者：
Stadnicka,A;Bosnjak,ZJ;Kampine,JP;Kwok,WM
内向整流 K+ 电流 (IKir) 是心肌静息电位的决定因素，其全身麻醉作用的细胞机制尚不完全清楚。因此，我们利用全细胞膜片钳技术研究了氟烷和异氟烷对豚鼠心室肌细胞 IKir 的影响。当膜电位为钾平衡电位的负值时，两种麻醉剂都会以浓度和电压依赖性方式降低稳态向内 IKir 的振幅。斜率电导降低，但内向电流的激活动力学没有改变。在钾平衡电位为正电位时，两种麻醉剂都会增加外向电流，这也会导致激活曲线出现小的去极化变化。当内部镁浓度较高时，异氟烷对外向电流的增加被消除，氟烷对内向电流的阻碍被减弱。在所有测试的膜电位下，精胺都能阻止两种麻醉剂对 IKir 的影响。结果显示挥发性麻醉剂对心脏 IKir 通道的电压依赖性调节。内向整流门控剂镁和精胺对麻醉效果的明显改变表明麻醉剂与 IKir 通道蛋白存在相互作用。 意义：在正常和改变的整流下，挥发性麻醉剂对心肌内向整流钾电流的差异调节可能有助于这些麻醉剂的心律失常作用机制。
The cellular mechanisms that underlie general anesthetic actions on the inward rectifier K+ current (IKir), a determinant of the resting potential in myocardium, are not fully understood. Using the whole-cell patch clamp technique, therefore, we investigated the effects of halothane and isoflurane on IKir in guinea pig ventricular myocytes. At membrane potentials negative to the equilibrium potential for potassium both anesthetics decreased amplitude of the steady-state inward IKir in a concentration-and voltage-dependent manner. The slope conductance was reduced, but the activation kinetics of the inward current were not altered. At potentials positive to the equilibrium potential for potassium, the outward current was increased by both anesthetics, which also caused small depolarizing shifts in the activation curve. With high internal magnesium concentration, the outward current increase by isoflurane was abolished, and the inward current block by halothane was attenuated. Spermine prevented the effects of both anesthetics on IKir at all membrane potentials tested. The results show voltage-dependent modulation of cardiac IKir channel by volatile anesthetics. Distinct modification of anesthetic effects by inward rectification gating agents, magnesium and spermine, suggests anesthetic interactions with the IKir channel protein.Implications:Differential modulation of myocardial inward rectifier potassium current by volatile anesthetics under normal and altered rectification may contribute to the mechanism of dysrhythmic actions by these anesthetics.