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Expression and relevance of the G protein-gated K+ channel in the mouse ventricle.
Scientific Reports ( IF 3.8 ) Pub Date : 2018-01-19 , DOI: 10.1038/s41598-018-19719-x
Allison Anderson , Kanchan Kulkarni , Ezequiel Marron Fernandez de Velasco , Nicholas Carlblom , Zhilian Xia , Atsushi Nakano , Kirill A. Martemyanov , Elena G. Tolkacheva , Kevin Wickman

The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1-/- or Girk4-/- mice. While loss of GIRK channels attenuated the CCh-induced shortening of action potential duration and suppression of ventricular myocyte excitability, selective ablation of GIRK channels in ventricle had no effect on heart rate, heart rate variability, or electrocardiogram parameters at baseline or after CCh injection. Additionally, loss of ventricular GIRK channels did not impact susceptibility to ventricular arrhythmias. These data suggest that the mouse ventricular GIRK channel is a GIRK1/GIRK4 heteromer, and show that while it contributes to the cholinergic suppression of ventricular myocyte excitability, this influence does not substantially impact cardiac physiology or ventricular arrhythmogenesis in the mouse.

中文翻译:

G蛋白门控的K +通道在小鼠心室中的表达及其相关性。

心房G蛋白门控的内向整流性K +(GIRK)通道是副交感神经对心脏生理影响的关键介质。在这里,我们探讨了小鼠心室中GIRK通道的细节和相关性。在小鼠心室中检测到较低水平的心房GIRK通道亚基(GIRK1,GIRK4),M2毒蕈碱受体(M 2 R)和RGS6(心房GIRK依赖性信号的负调节剂)的mRNA。胆碱能激动剂卡巴胆碱(CCh)激活了成年野生型心室肌细胞中的小GIRK电流,这些电流表现出相对较慢的动力学和较低的CCh敏感性。这些电流在Girk1 -/-或Girk4 -/-的心室肌细胞中不存在老鼠。虽然GIRK通道的丢失减弱了CCh诱导的动作电位持续时间的缩短和对心室肌细胞兴奋性的抑制,但在基线或CCh注射后,选择性消融心室中的GIRK通道对心率,心率变异性或心电图参数没有影响。此外,室性GIRK通道的丢失并不影响对室性心律不齐的敏感性。这些数据表明,小鼠心室GIRK通道是GIRK1 / GIRK4异源异构体,并且表明尽管它有助于胆碱能抑制心室肌细胞兴奋性,但这种影响基本上不会影响小鼠的心脏生理或心室心律失常。
更新日期:2018-01-19
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