The potassium current carried by TREK-1 channels in rat cardiac ventricular muscle
The potassium current carried by TREK-1 channels in rat cardiac ventricular muscle
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DOI：
10.1007/s00424-014-1678-9
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发表时间：
2015-05-01
影响因子：
4.5
通讯作者：
Daut, Juergen
中科院分区：
文献类型：
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作者：
Bodnar, Mandy;Schlichthoerl, Guenter;Daut, Juergen
我们研究了大鼠心室肌细胞TREK-1通道的钾电流。我们通过用阻断剂鸡尾酒阻断大多数其他通道将TREK-1电流与其他电流成分分离。我们试图通过用毛喉素和异丁基甲基黄嘌呤（IBMX）的混合物激活蛋白激酶A（PKA）来抑制TREK-1电流。PKA的激活阻断了膜电位为正至-40 mV时的外向整流电流分量。在37 A摄氏度，应用毛喉素加上IBMX减少了约52%的正电压下测得的稳态外向电流。应用钾通道阻滞剂奎尼丁或四己基铵也减少了约50%的稳态外向电流。总之，我们的结果表明，温度从22 A ℃升高到37 A ℃使TREK-1电流增加了至少5倍，并且大鼠心肌细胞中TREK-1电流在37 A ℃时的平均密度在+30 mV时约为1.5 pA/pF。采用动态膜片钳技术检测TREK-1对动作电位的影响。在减去模拟的TREK-1电流后，50或90%复极化的动作电位持续时间增加约12%，表明TREK-1可能在大鼠心室肌中具有重要的功能。在交感神经刺激过程中，通过PKA抑制TREK-1通道预期主要延长内膜下肌细胞的动作电位;这可能会降低复极的跨壁离散度，因此可能有助于预防心律失常的发生。
We studied the potassium current flowing through TREK-1 channels in rat cardiac ventricular myocytes. We separated the TREK-1 current from other current components by blocking most other channels with a blocker cocktail. We tried to inhibit the TREK-1 current by activating protein kinase A (PKA) with a mixture of forskolin and isobutyl-methylxanthine (IBMX). Activation of PKA blocked an outwardly rectifying current component at membrane potentials positive to -40 mV. At 37 A degrees C, application of forskolin plus IBMX reduced the steady-state outward current measured at positive voltages by about 52 %. Application of the potassium channel blockers quinidine or tetrahexylammonium also reduced the steady-state outward current by about 50 %. Taken together, our results suggest that the increase in temperature from 22 to 37 A degrees C increased the TREK-1 current by a factor of at least 5 and that the average density of the TREK-1 current in rat cardiomyocytes at 37 A degrees C is about 1.5 pA/pF at +30 mV. The contribution of TREK-1 to the action potential was assessed by using a dynamic patch clamp technique. After subtraction of simulated TREK-1 currents, action potential duration at 50 or 90 % repolarisation was increased by about 12 %, indicating that TREK-1 may be functionally important in rat ventricular muscle. During sympathetic stimulation, inhibition of TREK-1 channels via PKA is expected to prolong the action potential primarily in subendocardial myocytes; this may decrease the transmural dispersion of repolarisation and thus may serve to prevent the occurrence of arrhythmias.