Department of Electrical Engineering, Technical University of Denmark, Lyngby, Denmark.
Physiologisches Institut, Universität zu Lübeck, Lübeck, Germany.
Acta Physiol (Oxf). 2018 Jan;222(1). doi: 10.1111/apha.12906. Epub 2017 Jul 2.
Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles, but the exact mechanisms are still unknown.
To investigate the role of vascular gap junctions and potassium channels in the renal endothelial derived hyperpolarization.
In interlobar arteries from wild-type and connexin40 knockout mice, we assessed the role of calcium-activated small (SK) and intermediate (IK) conductance potassium channels. The role of inward rectifier potassium channels (Kir) and Na /K -ATPases was evaluated as was the contribution from gap junctions. Mathematical models estimating diffusion of ions and electrical coupling in myoendothelial gap junctions were used to interpret the results.
Lack of connexin40 significantly reduces renal endothelial hyperpolarization. Inhibition of SK and IK channels significantly attenuated renal EDH to a similar degree in wild-type and knockout mice. Inhibition of Kir and Na /K -ATPases affected the response in wild-type and knockout mice but at different levels of stimulation. The model confirms that activation of endothelial SK and IK channels generates a hyperpolarizing current that enters the vascular smooth muscle cells. Also, extracellular potassium increases sufficiently to activate Kir and Na /K -ATPases.
Renal endothelial hyperpolarization is mainly initiated by activation of IK and SK channels. The model shows that hyperpolarization can spread through myoendothelial gap junctions but enough potassium is released to activate Kir and Na /K -ATPases. Reduced coupling seems to shift the signalling pathway towards release of potassium. However, an alternative pathway also exists and needs to be investigated.
探讨血管缝隙连接和钾通道在肾脏内皮衍生超极化中的作用。
在野生型和连接蛋白 40 敲除小鼠的叶间动脉中，我们评估了钙激活的小（SK）和中间（IK）电导钾通道的作用。评估了内向整流钾通道（Kir）和 Na+/K+-ATP 酶的作用，以及缝隙连接的贡献。用于解释结果的数学模型估计了离子在肌内皮缝隙连接中的扩散和电耦联。
缺乏连接蛋白 40 显著减少了肾脏内皮超极化。在野生型和敲除小鼠中，SK 和 IK 通道的抑制显著减弱了肾脏 EDH 的作用。Kir 和 Na+/K+-ATP 酶的抑制对野生型和敲除小鼠的反应有影响，但在不同的刺激水平上。该模型证实，内皮 SK 和 IK 通道的激活产生了进入血管平滑肌细胞的超极化电流。此外，细胞外钾的增加足以激活 Kir 和 Na+/K+-ATP 酶。
肾脏内皮超极化主要由 IK 和 SK 通道的激活引发。该模型表明，超极化可以通过肌内皮缝隙连接传播，但释放的钾足以激活 Kir 和 Na+/K+-ATP 酶。耦合减少似乎将信号通路转向钾的释放。然而，还存在另一种途径，需要进一步研究。
