A mathematical model of the rat kidney IV: whole-kidney response to hyperkalemia

The renal response to acute hyperkalemia is mediated by increased K secretion within connecting tubule (CNT), flux that is modulated by tubular effects (e.g. aldosterone) in conjunction with increased luminal flow. There is ample evidence that peritubular K blunts Na reabsorption in proximal tubule, thick ascending Henle limb, and distal convoluted tubule (DCT). While any such reduction may augment CNT delivery, the relative contribution of each is uncertain. The kidney model of this lab was recently advanced with representation of cortical labyrinth and medullary ray. Model tubules capture the impact of hyperkalemia to blunt Na reabsorption within each upstream segment. However, this forces the question of the extent to which increased Na delivery is transmitted past macula densa and its tubuloglomerular feedback (TGF) signal. Beyond increasing macula densa Na delivery, peritubular K is predicted to raise cytosolic Cl and depolarize macula densa cells, which may also activate TGF. Thus, although upstream reduction in Na transport may be larger, it appears that the DCT effect is critical to increasing CNT delivery. Beyond the flow effect, hyperkalemia reduces ammoniagenesis and reduced ammoniagenesis enhances K excretion. What this model provides is a possible mechanism. When cortical NH4 is taken up via peritubular Na,K(NH4)-ATPase, it acidifies principal cells. Consequently, reduced ammoniagenesis increases principal cell pH, thereby increasing conductance of both ENaC and ROMK, enhancing K excretion. In this model, aldosterone's effect on principal cells, diminished DCT Na reabsorption, and reduced ammoniagenesis, all provide relatively equal and additive contributions to renal K excretion.

Wpływ pandemii COVID-19 na funkcjonowanie regionalnego transportu kolejowego obszarów przygranicznych – na przykładzie województwa dolnośląskiego (PL) i kraju libereckiego (CZ)

Systemy zbiorowego transportu publicznego są narażone na wiele zewnętrznych czynników wpływających na ich funkcjonowanie. Jednym z nich może być zagrożenie epidemiologiczne. W 2020 r. światowa pandemia COVID-19 miała istotny wpływ na światową gospodarkę oraz przewozy pasażerskie. Wprowadzone liczne ograniczenia wpłynęły na popyt (liczbę pasażerów) oraz podaż (oferta przewozowa) na rynku transportu. Do najczęstszych obostrzeń zaliczyć można: ograniczenie liczby połączeń, zmniejszenie limitu pasażerów w pojeździe, ograniczenie siatki połączeń komunikacyjnych. W analizie autorzy przeprowadzili badanie województwa dolnośląskiego oraz kraju libereckiego w kontekście zmian w funkcjonowaniu regionalnego transportu kolejowego. Spadek liczby kursów dotyczył nie tylko linii peryferyjnych (kraj liberecki), ale również głównych tras w regionie (Dolny Śląsk). W Czechach alternatywnym środkiem transportu mogły być przewozy autobusowe. Powrót do poziomu stanu sprzed ograniczeń przewozowych powinien być związany z zachęcaniem pasażerów do ponownego korzystania z transportu kolejowego. Długotrwały spadek poziomu obsługi komunikacyjnej mógł skłonić mieszkańców do wyboru alternatywnych środków transportu (np. samochód). Stabilność oferty przewozowej stanowi jeden z filarów wysokiego popytu na transport publiczny. Czynnik zewnętrzny (pandemia) nie powinien być powodem radykalnych redukcji siatki połączeń. W niektórych przypadkach może to przynosić odwrotne skutki, np. wzrost zatłoczenia w godzinach szczytu (dojazdy do pracy). Analiza wykazała, że skoordynowane (zintegrowane) systemy transportu publicznego są lepiej przygotowane na potencjalne zagrożenia zewnętrzne niż model oparty na słabej pozycji organizatora przewozów. W Polsce samorząd wojewódzki ma duży wpływ na transport kolejowy, ale bardzo słaby na przewozy autobusowe. Model czeski z kolei oparty jest na regionalnej koordynacji obu środków transportu.

Catalytic Asymmetry in Homodimeric H+-Pumping Membrane Pyrophosphatase Demonstrated by Non-Hydrolyzable Pyrophosphate Analogs

Membrane-bound inorganic pyrophosphatase (mPPase) resembles the F-ATPase in catalyzing polyphosphate-energized H+ and Na+ transport across lipid membranes, but differs structurally and mechanistically. Homodimeric mPPase likely uses a “direct coupling” mechanism, in which the proton generated from the water nucleophile at the entrance to the ion conductance channel is transported across the membrane or triggers Na+ transport. The structural aspects of this mechanism, including subunit cooperation, are still poorly understood. Using a refined enzyme assay, we examined the inhibition of K+-dependent H+-transporting mPPase from Desulfitobacterium hafniensee by three non-hydrolyzable PPi analogs (imidodiphosphate and C-substituted bisphosphonates). The kinetic data demonstrated negative cooperativity in inhibitor binding to two active sites, and reduced active site performance when the inhibitor or substrate occupied the other active site. The nonequivalence of active sites in PPi hydrolysis in terms of the Michaelis constant vanished at a low (0.1 mM) concentration of Mg2+ (essential cofactor). The replacement of K+, the second metal cofactor, by Na+ increased the substrate and inhibitor binding cooperativity. The detergent-solubilized form of mPPase exhibited similar active site nonequivalence in PPi hydrolysis. Our findings support the notion that the mPPase mechanism combines Mitchell’s direct coupling with conformational coupling to catalyze cation transport across the membrane.

Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice

We compared the regulation of the NaCl cotransporter (NCC) in adaptation to a low-K (LK) diet in male and female mice. We measured hydrochlorothiazide (HCTZ)-induced changes in urine volume (UV), glomerular filtration rate (GFR), absolute (ENa, EK), and fractional (FENa, FEK) excretion in male and female mice on control-K (CK, 1% KCl) and LK (0.1% KCl) diets for 7 days. With CK, NCC-dependent ENa and FENa were larger in females than males as observed previously. However, with LK, HCTZ-induced ENa and FENa increased in males but not in females, abolishing the sex differences in NCC function as observed in CK group. Despite large diuretic and natriuretic responses to HCTZ, EK was only slightly increased in response to the drug when animals were on LK. This suggests that the K-secretory apparatus in the distal nephron is strongly suppressed under these conditions. We also examined LK-induced changes in Na transport protein expression by Western blotting. Under CK conditions females expressed more NCC protein, as previously reported. LK doubled both total (tNCC) and phosphorylated NCC (pNCC) abundance in males but had more modest effects in females. The larger effect in males abolished the sex-dependence of NCC expression, consistent with the measurements of function by renal clearance. LK intake did not change NHE3, NHE2, or NKCC2 expression, but reduced the amount of the cleaved (presumably active) form of γENaC. LK reduced plasma K to lower levels in females than males. These results indicated that males had a stronger NCC-mediated adaptation to LK intake than females.

Genetic Diversity and Synergistic Modulation of Salinity Tolerance Genes in Aegilops tauschii Coss

Aegilops tauschii Coss. (2n = 2x = 14, DD) is a problematic weed and a rich source of genetic material for wheat crop improvement programs. We used physiological traits (plant height, dry weight biomass, Na+ and K+ concentration) and 14 microsatellite markers to evaluate the genetic diversity and salinity tolerance in 40 Ae. tauschii populations. The molecular marker allied with salinity stress showed polymorphisms, and a cluster analysis divided the populations into different groups, which indicated diversity among populations. Results showed that the expression level of AeHKT1;4 and AeNHX1 were significantly induced during salinity stress treatments (50 and 200 mM), while AeHKT1;4 showed relative expression in roots, and AeNHX1 was expressed in leaves under the control conditions. Compared with the control conditions, the expression level of AeHKT1;4 significantly increased 1.7-fold under 50 mM salinity stress and 4.7-fold under 200 mM salinity stress in the roots of Ae. tauschii. AeNHX1 showed a relative expression level of 1.6-fold under 50 mM salinity stress and 4.6-fold under 200 mM salinity stress compared with the control conditions. The results provide strong evidence that, under salinity stress conditions, AeHKT1;4 and AeNHX1 synergistically regulate the Na+ homeostasis through regulating Na+ transport in Ae. tauschii. AeNHX1 sequestrated the Na+ into vacuoles, which control the regulation of Na+ transport from roots to leaves under salinity stress conditions in Ae. tauschii.