The potassium current carried by TREK-1 channels in rat cardiac ventricular muscle

被引:14
作者
Bodnar, Mandy [1 ]
Schlichthoerl, Guenter [1 ]
Daut, Juergen [1 ]
机构
[1] Univ Marburg, Inst Physiol & Pathophysiol, D-35037 Marburg, Germany
来源
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY | 2015年 / 467卷 / 05期
关键词
K-2P-channels; Action potential duration; Dispersion of repolarisation; Protein kinase A; ACTION-POTENTIAL DURATION; K+ CHANNEL; MECHANOELECTRIC FEEDBACK; DIFFERENTIAL EXPRESSION; FUNCTIONAL EXPRESSION; DYNAMIC CLAMP; QT SYNDROME; MYOCYTES; HEART; REPOLARIZATION;
D O I
10.1007/s00424-014-1678-9
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:1069 / 1079
页数:11
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