Renal potassium channels: function, regulation, and structure

Many transport functions in renal tubules depend on potassium (K) channels. Not only does K secretion and the maintenance of external K balance depend on K channel activity in principal tubule cells, but K channels also regulate cell volume; they are an integral party of cell function in all tubule cells because of their key role in the generation of the cell-negative electrical potential that affects the transmembrane movement of many charged solutes. Moreover, the recycling of K across the apical membrane of the thick ascending limb (TAL) plays an important role in the control of NaCl reabsorption in this tubule segment. Significant progress in our understanding of the structure and function of renal K channels has become possible by combining several strategies. These include transport studies in single tubules, application of the patch-clamp technique for exploring the properties of single K channels in native tubules and the cloning, and expression of diverse K channels of renal origin. Insights from these investigations promise to provide a deeper understanding of the mechanism by which K channels participate in many diverse tubule functions.     

Polycystin: new aspects of structure, function, and regulation

Polycystin-1 is a modular membrane protein with a long extracellular N-terminal portion that bears several ligand-binding domains, 11 transmembrane domains, and a > or =200 amino acid intracellular C-terminal portion with several phosphorylation signaling sites. Polycystin-1 is highly expressed in the basal membranes of ureteric bud epithelia during early development of the metanephric kidney, and disruption of the PKD1 gene in mice leads to cystic kidneys and embryonic or perinatal death. It is proposed that polycystin-1 functions as a matrix receptor to link the extracellular matrix to the actin cytoskeleton via focal adhesion proteins. Co-localization, co-sedimentation, and co-immunoprecipitation studies show that polycystin-1 forms multiprotein complexes with alpha2beta1-integrin, talin, vinculin, paxillin, p130cas, focal adhesion kinase, and c-src in normal human fetal collecting tubules and sub-confluent epithelial cultures. In normal adult kidneys and confluent epithelial cultures, polycystin-1 is downregulated and forms complexes with the cell-cell adherens junction proteins E-cadherin and beta-, gamma-, and alpha-catenin. Polycystin-1 activation at the cell membrane leads to intracellular signaling via phosphorylation through the c-Jun terminal kinase and wnt pathways leading to activation of AP-1 and TCF/LEF-dependent genes, respectively. The C-terminal of polcystin-1 has been shown to be phosphorylated by c-src at Y4237, by protein kinase A at S4252, and by focal adhesion kinase and protein kinase X at yet-to-be identified residues. Inhibition of tyrosine phosphorylation or increased cellular calcium increases polycystin-1 focal adhesion complexes versus polycystin-1 adherens junction complexes, whereas disruption of the actin cytoskeleton dissociates all polycystin-1 complexes. Genetic evidence suggests that PKD1, PKD2, NPHP1, and tensin are in the same pathway.     

Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men

Previous studies demonstrated that the administration of NaHCO3 or sodium citrate had either only a small effect to reduce urinary Ca excretion or no effect, but that potassium citrate significantly reduced urinary Ca excretion. In order to further evaluate and compare the effects of NaHCO3 and of KHCO3, we performed ten metabolic balances in healthy men during 18 control days, 12 days of NaHCO3, 60 mmol/day and 12 days of KHCO3, 60 mmol/day. Six subjects were fed a low Ca diet (5.2 +/- 0.7 SD mmol/day) and three of these were also given calcitriol (0.5 microgram 6-hourly). Four subjects ate a normal Ca diet (19.5 +/- 1.3 mmol/day). For all 10 subjects, KHCO3 administration reduced urinary Ca excretion from control by -0.9 +/- 0.7 mmol/day, P less than 0.001. Net intestinal Ca absorption did not change detectably so that Ca balances became less negative by a +0.9 +/- 0.9 mmol/day; P = 0.01. KHCO3 administration was also accompanied by more positive PO4 and Mg balances. NaHCO3 administration had no significant effect on urinary Ca excretion or Ca balance. NaHCO3 and KHCO3 administration were accompanied by equivalently more positive Na or K balances, respectively and equivalently more negative acid balances (HCO3 retention). Neither NaHCO3 or KHCO3 altered fasting serum HCO3 concentrations, blood pH, serum 1,25-(OH)2-D or PTH concentrations. We conclude that KHCO3 promotes more positive Ca balances by either enhancing renal Ca retention or skeletal Ca retention or both.     

碳酸氢钠水化方案预防冠状动脉造影术后对比剂肾病的研究

目的探讨碳酸氢钠水化方案对冠状动脉造影术后对比剂肾病(contrast-induced nephropathy,CIN)的预防作用。方法选取2013年7月至2015年7月在我院心血管内科行冠脉造影术的患者245例为研究对象,随机分为观察组123例以及对照组122例。观察组患者造影术前1 h按3 ml·kg~(-1)·h~(-1)速度静脉输注1.25%碳酸氢钠注射液,对照组造影术前1 h按3 ml·kg~(-1)·h~(-1)速度静脉输注0.9%氯化钠注射液。对比分析2组术前、术后24 h、48 h共3次血肌酐(SCr)、钾离子(K~+)、碳酸氢根(HCO_3~-)、肾小球滤过率(glomerular filtration rate,GFR)、尿液pH值、尿转铁蛋白(transferrin,TRF)、胱抑素C(cystatin C,Cys C)及同型半胱氨酸(homocysteine,Hcy)的差异。结果观察组患者CIN发生率、二级终点事件发生率及需要行血液透析的比例分别为2.44%、0.00%、0.00%,显著低于对照组11.47%、5.74%、4.92%,差异有统计学意义(P0.05)。观察组术后24 h的SCr、Cys C、Hcy水平分别为(82.28±22.16)μmol/L、(1.24±0.21)mg/L、(14.02±3.14)μmol/L,术后48 h分别为(82.06±22.79)μmol/L、(0.82±0.11)mg/L、(8.02±2.45)μmol/L,显著低于术前(94.58±17.63)μmol/L、(1.98±0.25)mg/L、(17.25±4.28)μmol/L,GFR、HCO_3~-、K~+、TRF水平术后24 h分别为(99.04±28.53)ml·min~(-1)·(1.73 m~2)~(-1)、(26.09±2.99)mmol/L、(5.22±0.34)mmol/L、(4.82±0.52)mg/L,术后48 h分别为(102.34±38.49)ml·min~(-1)·(1.73 m~2)~(-1)、(25.72±2.30)mmol/L、(6.02±0.50)mmol/L、(5.38±0.64)mg/L,显著高于术前(79.93±18.14)ml·min~(-1)·(1.73 m~2)~(-1)、(24.03±4.18)mmol/L、(3.88±0.31)mmol/L、(2.69±0.48)mg/L,而对照组术后24 h SCr、GFR、HCO_3~-、K~+、TRF水平分别为(92.79±29.04)μmol/L、(85.64±34.88)ml·min~(-1)·(1.73 m~2)~(-1)、(24.17±4.04)mmol/L、(4.02±0.26)mmol/L、(2.92±0.64)mg/L,术后48 h分别为(93.89±25.75)μ.mol/L、(90.88±29.39)ml·min~(-1)·(1.73 m2)~(-1)、(23.81±4.18)mmol/L、(4.25±0.33)mmol/L、(3.08±0.71)mg/L,与治疗前的(94.97士22.79)μmol/L、(79.51±20.34)ml·min~(-1)·(1.73 m2)~(-1)、(24.01±3.17)mmol/L、(3.91±0.35)mmol/L、(2.71±0.52)mg/L比较无变化,差异无统计学意义(P0.05)。结论对冠状动脉造影术后造影患者使用碳酸氢钠水化干预能降低CIN的发生率,有效地保护肾脏功能。     

The prevention of pain from injection of rocuronium by magnesium sulphate,lignocaine, sodium bicarbonate and alfentanil

We compared the efficacy of magnesium sulphate, lignocaine, sodium bicarbonate or alfentanil in minimizing pain due to injection of rocuronium in 250 patients. After tourniquet application on the forearm, the patients were given saline, magnesium sulphate, lignocaine, sodium bicarbonate 8.4% or alfentanil, diluted into a 3 ml solution. The occlusion was released after 20 seconds, and rocuronium was injected over 10 to 15 seconds. The patients were observed and asked immediately if they had pain in the arm and the response was assessed. Reactions such as discomfort and pain, withdrawal of the hand and screaming after the administering of the rocuronium were recorded as side-effects and patients were reassessed at 24 hours postoperatively. We concluded that magnesium sulphate, lignocaine, sodium bicarbonate or alfentanil decreased the level of rocuronium injection pain. Of these drugs, magnesium sulphate, lignocaine and sodium bicarbonate were the most effective while alfentanil was the least effective.     

The labrum: structure, function, and injury with femoro-acetabular impingement

Background

The recognition of the importance of femoro-acetabular impingement (FAI) as a potential cause of hip pain has been stimulated by major efforts to salvage hip joints by reconstruction to prevent or delay the need for replacement. A previous review addressed the nature of FAI, the various types, and how to make the diagnosis. When FAI occurs, the structure between the femur and acetabular rim, the labrum, is initially impinged upon and subsequently injured.

Method

Injury to the labrum should be recognized when treating the osseous causes of FAI. Preserving or recovering labral function, enhancing hip stability and protecting the articular surface, is critical to restoring the hip to normal or near-normal mechanical and physiologic function. The present review collected the varied essential information about the labrum in a succinct manner, independent of treatment algorithms.

Results/conclusion

Advanced knowledge of the labrum is presented, including the anatomy, circulation, histology, embryology, and neurology, as well as how the labrum tears, the types of tears, and how to make the diagnosis. The advantages and limitations of diagnostic magnetic resonance techniques are discussed, including magnetic resonance imaging (MRI), indirect magnetic resonance arthrography (i-MRA), and direct magnetic resonance arthrography (d-MRA). The review recognizes the complexity of the labrum and provides a greater understanding of how the labrum is capable of stabilizing the joint and protecting the articular surface of the hip. This information will act as a guide in developing treatment plans when treating FAI.     

The foetal Leydig cell-- differentiation, function and regulation

The foetal Leydig cell population arises shortly after testicular differentiation at around 12.5 dpc in the mouse and 6 weeks in the human. These cells function, primarily, to produce androgens which are essential for masculinization of the foetus. The origin of the foetal Leydig cells remains uncertain but it has been suggested that adrenocortical cells and foetal Leydig cells may share a common origin in an adreno-genital primordium. Studies in the mouse are beginning to identify factors such as desert hedgehog and platelet-derived growth factor which are required for foetal Leydig cell development. Regulation of foetal Leydig cell function remains uncertain in most species. Unlike the adult population of Leydig cells, the foetal Leydig cells in the mouse do not require luteinizing hormone (LH) to stimulate androgen production. An intact pituitary does appear to be required, however, and adrenocorticotrophic hormone (ACTH) will stimulate foetal Leydig cell function directly suggesting that both LH and ACTH act to maintain Leydig cell function in vivo. In the human LH/hCG is required for foetal Leydig cell function although the cells may also be sensitive to ACTH.     

Use of N-acetylcholine and sodium bicarbonate to protect renal transplant function during endovascular renal artery aneurysm exclusion

We describe the successful use of hydration with sodium bicarbonate and N-acetylcholine to prevent contrast-induced nephrophathy in a patient with a kidney transplant undergoing endovascular native renal artery aneurysm exclusion. The implications for surveillance studies for endovascular procedures are discussed.     

ORIGINAL ARTICLE: Potency and recovery characteristics of rocuronium mixed with sodium bicarbonate

Sodium bicarbonate may be added to rocuronium to decrease pain on injection. However, this mixture may result in the formation of carbon dioxide bubbles. We investigated whether the addition of sodium bicarbonate to rocuronium alters neuromuscular blockade, in 120 patients randomly assigned to receive rocuronium mixed with saline or bicarbonate 8.4%, either in varying doses (for dose‐response measurements; 60 patients) or a fixed dose of 600 μg.kg^‐1 (for time‐course measurements; 60 patients). Sodium bicarbonate resulted in a left‐shift of the rocuronium dose‐response curve. The effective doses of rocuronium to produce 95% twitch depression were 331.6 (95% CI: 310.4–352.8) and 284.3 (95% CI: 262.0–306.6) μg.kg^?1 mixed with isotonic saline or sodium bicarbonate, respectively (p < 0.001). The mean (SD) onset times of rocuronium 600 μg.kg^‐1 were 3.6 (0.6) and 2.7 (0.5) min in the corresponding groups, respectively (p < 0.001). The mean (SD) times to 95% recovery were 35.8 (5.8) and 47.9 (7.1) min, respectively (p < 0.001). We conclude that the mixing of sodium bicarbonate with rocuronium enhances the potency, shortens the onset and prolongs the duration of action.     

Primary active sodium transport, oxygen consumption, and ATP: coupling and regulation

Several metabolic aspects of primary active transport have been explored in this communication. One emphasized theme entailed the need to investigate the properties of the mitochondria and the active transport systems within the intact cell. Several methodological and conceptual approaches were described that permitted such an analysis. The answers provided were sometimes qualitative or quantitative. Qualitative information was provided regarding the cytosolic signal linking active transport with respiration, suggesting that the cytosolic ADP concentration was an important element in that link. The intact renal cell was found to work normally at 50 to 60% of its maximal respiratory capacity, indicating that sufficient reserve capacity was present for increased metabolic demands. Several examples were described in which a combination of qO2 measurements and/or optical techniques were used to differentiate between effects of agents which act primarily on transport or metabolic events. Finally, the control of transport by metabolism was discussed, primarily emphasizing the role of ATP and Pi. One of the overall conclusions from these studies is that, in general, the mitochondria and the transport systems seem to display similar properties in the intact cell as they do in isolated form. However, uncertainties concerning the cellular microenvironment surrounding the mitochondria and the plasma membrane transporters have produced some interesting surprises concerning their function in the intact cell. More quantitative information on the energy compartmentation of the renal cell would be helpful to clarify numerous aspects of metabolic function.