Chen Pei, Guzman John P, Leong Patrick K K, Yang Li E, Perianayagam Anjana, Babilonia Elisa, Ho Jennifer S, Youn Jang H, Wang Wen Hui, McDonough Alicia A
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 1333 San Pablo St., Los Angeles, CA 90089-9142, USA.
Am J Physiol Cell Physiol. 2006 May;290(5):C1355-63. doi: 10.1152/ajpcell.00501.2005. Epub 2005 Dec 14.
Extracellular K(+) concentration ([K(+)]) is closely regulated by the concerted regulatory responses of kidney and muscle. In this study, we aimed to define the responses activated when dietary K(+) was moderately reduced from a control diet (1.0% K(+)) to a 0.33% K(+) diet for 15 days. Although body weight and baseline plasma [K(+)] (4.0 mM) were not reduced in the 0.33% K(+) group, regulatory responses to conserve plasma [K(+)] were evident in both muscle and kidney. Insulin-stimulated clearance of K(+) from the plasma was estimated in vivo in conscious rats with the use of tail venous and arterial cannulas. During infusion of insulin.(50 mU.kg(-1).min(-1)), plasma [K(+)] level fell to 3.2 +/- 0.1 mM in the 1.0% K(+) diet group and to only 3.47 +/- 0.07 mM in the 0.33% K(+) diet group (P < 0.01) with no reduction in urinary K(+) excretion, which is evidence of insulin resistance to cellular K(+) uptake. Insulin-stimulated cellular K(+) uptake was quantitated by measuring the K(+) infusion rate necessary to clamp plasma K(+) at baseline (in micromol.kg(-1).min(-1)) during 5 mU of insulin.kg(-1).min(-1) infusion: 9.7 +/- 1.5 in 1% K(+) diet was blunted to 5.2 +/- 1.7 in the 0.33% K(+) diet group (P < 0.001). Muscle [K(+)] and Na(+)-K(+)-ATPase activity and abundance were unchanged during the 0.33% K(+) diet. Renal excretion, which was measured overnight in metabolic cages, was reduced by 80%, from 117.6 +/- 10.5 micromol/h/animal (1% K(+) diet) to 24.2 +/- 1.7 micromol/h/animal (0.33% K(+) diet) (P < 0.001). There was no significant change in total abundance of key renal K(+) transporters, but 50% increases in both renal PTK cSrc abundance and ROMK phosphorylation in the 0.33% K(+) vs. 1% K(+) diet group, previously established to be associated with internalization of ROMK. These results indicate that plasma [K(+)] can be maintained during modest K(+) restriction due to a decrease in insulin-stimulated cellular K(+) uptake as well as renal K(+) conservation mediated by inactivation of ROMK, both without a detectable change in plasma [K(+)]. The error signals inciting and maintaining these responses remain to be identified.
细胞外钾离子浓度（[K⁺]）受到肾脏和肌肉协同调节反应的密切调控。在本研究中，我们旨在明确当饮食中的钾离子从对照饮食（1.0% K⁺）适度减少至0.33% K⁺饮食并持续15天时所激活的反应。尽管0.33% K⁺组的体重和基线血浆[K⁺]（4.0 mM）未降低，但肌肉和肾脏中保存血浆[K⁺]的调节反应均很明显。利用尾静脉和动脉插管在清醒大鼠体内估计胰岛素刺激的血浆钾离子清除率。在输注胰岛素（50 mU·kg⁻¹·min⁻¹）期间，1.0% K⁺饮食组的血浆[K⁺]水平降至3.2±0.1 mM，而0.33% K⁺饮食组仅降至3.47±0.07 mM（P<0.01），同时尿钾排泄未减少，这是胰岛素对细胞摄取钾离子产生抵抗的证据。通过测量在输注5 mU胰岛素·kg⁻¹·min⁻¹期间将血浆钾离子钳制在基线水平（以微摩尔·kg⁻¹·min⁻¹计）所需的钾离子输注速率来定量胰岛素刺激的细胞钾离子摄取：1% K⁺饮食组为9.7±1.5，在0.33% K⁺饮食组中降至5.2±1.7（P<0.001）。在0.3% K⁺饮食期间，肌肉[K⁺]、钠钾ATP酶活性和丰度未发生变化。在代谢笼中过夜测量的肾脏排泄量减少了80%，从117.6±10.5微摩尔/小时/动物（1% K⁺饮食）降至24.2±1.7微摩尔/小时/动物（0.33% K⁺饮食）（P<0.001）。关键肾脏钾离子转运体的总丰度无显著变化，但与1% K⁺饮食组相比，0.33% K⁺饮食组的肾脏PTK cSrc丰度和ROMK磷酸化均增加了50%，此前已确定这与ROMK的内化有关。这些结果表明，在适度限钾期间，由于胰岛素刺激的细胞钾离子摄取减少以及ROMK失活介导的肾脏钾离子保存，血浆[K⁺]得以维持，而血浆[K⁺]均无可检测到的变化。引发和维持这些反应的误差信号仍有待确定。
