Control of capillary hydraulic conductivity via membrane potential-dependent changes in Ca2+ influx

1992 ◽  
Vol 262 (1) ◽  
pp. H144-H148 ◽  
Author(s):  
R. S. Zhang ◽  
V. H. Huxley

Capillary permeability has been shown to be sensitive to the levels of intracellular calcium. We examined the role of membrane potential in the regulation of capillary water permeability by a Ca2+ leak mechanism. Repeated measures of Lp were taken in situ on individually perfused mesenteric capillaries of cerebrally pithed frogs (Rana pipiens). A rise in extracellular potassium ([K+]o) to 24 mM induced a 45% decrease in Lp (n = 20), whereas lowering [K+]o to 0.24 mM elevated Lp by twofold (n = 9). To investigate whether these changes in Lp were due specifically to changes in membrane potential and consequent changes in the driving force for Ca2+ influx, we performed the following experiments: 1) [K+]o was elevated while the product of [K+]o and extracellular chloride concentration [Cl-]o was kept constant, 2) [K+]o was elevated under nominally Ca(2+)-free conditions, 3) K+ leak was induced by addition of 10 microM valinomycin, and 4) Na(+)-K+ pump was blocked by 10 microM ouabain. A constant [K+]o [Cl-]o product did not prevent high K+ from lowering Lp. Nominally Ca(2+)-free conditions abolished the effect of high K+. Valinomycin mimicked the response to low K+, and ouabain failed to change Lp. The data from this study conform to the hypothesis that membrane potential is an important regulator of capillary barrier properties via changes in Ca2+ influx through leak channels.

1998 ◽  
Vol 330 (3) ◽  
pp. 1283-1291 ◽  
Author(s):  
Richard POULIN ◽  
Chenqi ZHAO ◽  
Savita VERMA ◽  
René CHAREST-GAUDREAULT ◽  
Marie AUDETTE

The mechanism of mammalian polyamine transport is poorly understood. We have investigated the role of plasma-membrane potential (ΔΨpm) in putrescine and spermidine uptake in ZR-75-1 human breast cancer cells. The rate of [3H]putrescine and [3H]spermidine uptake was inversely correlated to extracellular [K+] ([K+]o) and to ΔΨpm, as determined by the accumulation of [3H]tetraphenylphosphonium bromide (TPP). Inward transport was unaffected by a selective decrease in mitochondrial potential (ΔΨmit) induced by valinomycin at low [K+]o, but was reduced by ≈ 60% by the rheogenic protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP), which rapidly (≤ 15 min) collapsed both ΔΨpm and ΔΨmit. Plasma-membrane depolarization by high [K+]o or CCCP did not enhance putrescine efflux in cells pre-loaded with [3H]putrescine, suggesting that decreased uptake caused by these agents did not result from a higher excretion rate. On the other hand, the electroneutral K+/H+ exchanger nigericin (10 μM) co-operatively depressed [3H]TPP, [3H]putrescine and [3H]spermidine uptake in the presence of ouabain. Suppression of putrescine uptake by nigericin+ouabain was Na+-dependent, suggesting that plasma-membrane repolarization by the electrogenic Na+ pump was required upon acidification induced by nigericin, due to the activation of the Na+/H+ antiporter. The sole addition of 5-N,N-hexamethylene amiloride, a potent inhibitor of the Na+/H+ antiporter, strongly inhibited putrescine uptake in a competitive fashion [Ki 4.0±0.9 (S.D.) μM], while being a weaker antagonist of spermidine uptake. The potency of a series of amiloride analogues to inhibit putrescine uptake was clearly different from that of the Na+/H+ antiporter, and resembled that noted for Na+ co-transport proteins. These data demonstrate that putrescine and spermidine influx is mainly unidirectional and strictly depends on ΔΨpm, but not ΔΨmit. This report also provides first evidence for a high-affinity amiloride-binding site on the putrescine carrier, which provides new insight into the biochemical properties of this transporter.


2011 ◽  
Vol 20 (01) ◽  
pp. 95-103 ◽  
Author(s):  
S. OKTYABRSKY ◽  
P. NAGAIAH ◽  
V. TOKRANOV ◽  
M. YAKIMOV ◽  
R. KAMBHAMPATI ◽  
...  

Hall electron mobility in buried QW InGaAs channels, grown on InP substrates with HfO 2 gate oxide, is analyzed experimentally and theoretically as a function of top barrier thickness and composition, carrier density, and temperature. Temperature slope α in μ ~Tα dependence is changing from α=-1.1 to +1 with the reduction of the top barrier thickness indicating the dominant role of remote Coulomb scattering (RCS) in interface-related contribution to mobility degradation. Insertion of low-k SiO x interface layer formed by oxidation of thin in-situ MBE grown amorphous Si passivation layer has been found to improve the channel mobility, but at the expense of increased EOT. This mobility improvement is also consistent with dominant role of RCS. We were able to a obtain a reasonable match between experiment and simple theory of the RCS assuming the density of charges at the high-k/barrier interface to be in the range of (2-4)×1013 cm-2.


2006 ◽  
Vol 914 ◽  
Author(s):  
Mikhail Baklanov ◽  
David O'Dwyer ◽  
Adam M Urbanowicz ◽  
Quoc Toan Le ◽  
Steven Demuynck ◽  
...  

AbstractInteraction of moisture with porous low-k films is evaluated by using in situ ellipsometry setup. The adsorbed water amount is calculated from change of refractive index measured during the adsorption. Pristine low-k films reversibly adsorb 2 - 5% of water that reflects presence of constitutive hydrophilic centrums. Plasma and thermal treatments increase the number of hydrophilic centrums. Once the amount of these centrums has reached a certain critical value sufficient to form a continuous water film, bulk water condensation is observed. Change of properties during the water adsorption in the damaged films is not fully reversible. Each additional adsorption cycle increases the dielectric function of the film because of decreasing porosity, increasing skeleton density and shrinkage. The pressure corresponding to the bulk condensation allows us to calculate internal contact angle (internal surface energy) of low-k materials. The water molecules adsorbed on separate OH groups play the role of a catalyst that hydrolyses the siloxane bridges initially present on hydrophobic surface.


2020 ◽  
Vol 319 (2) ◽  
pp. F323-F334
Author(s):  
Lei Yang ◽  
Gustavo Frindt ◽  
Yuanyuan Xu ◽  
Shinichi Uchida ◽  
Lawrence G. Palmer

We investigated the regulation of Na+ and K+ excretion and the epithelial Na+ channel (ENaC) in mice lacking the gene for aldosterone synthase (AS) using clearance methods to assess excretion and electrophysiology and Western blot analysis to test for ENaC activity and processing. After 1 day of dietary Na+ restriction, AS−/− mice lost more Na+ in the urine than AS+/+ mice did. After 1 wk on this diet, both genotypes strongly reduced urinary Na+ excretion, but creatinine clearance decreased only in AS−/− mice. Only AS+/+ animals exhibited increased ENaC function, assessed as amiloride-sensitive whole cell currents in collecting ducts or cleavage of αENaC and γENaC in Western blots. To assess the role of aldosterone in the excretion of a K+ load, animals were fasted overnight and refed with high-K+ or low-K+ diets for 5 h. Both AS+/+ and AS−/− mice excreted a large amount of K+ during this period. In both phenotypes the excretion was benzamil sensitive, indicating increased K+ secretion coupled to ENaC-dependent Na+ reabsorption. However, the increase in plasma K+ under these conditions was much larger in AS−/− animals than in AS+/+ animals. In both groups, cleavage of αENaC and γENaC increased. However, Na+ current measured ex vivo in connecting tubules was enhanced only in AS+/+ mice. We conclude that in the absence of aldosterone, mice can conserve Na+ without ENaC activation but at the expense of diminished glomerular filtration rate. Excretion of a K+ load can be accomplished through aldosterone-independent upregulation of ENaC, but aldosterone is required to excrete the excess K+ without hyperkalemia.


2014 ◽  
Vol 306 (1) ◽  
pp. F53-F60 ◽  
Author(s):  
Dao-Hong Lin ◽  
Peng Yue ◽  
Chengbiao Zhang ◽  
Wen-Hui Wang

The aim of the study is to explore the role of miR-194 in mediating the effect of high-K (HK) intake on ROMK channel. Northern blot analysis showed that miR-194 was expressed in kidney and that HK intake increased while low-K intake decreased the expression of miR-194. Real-time PCR analysis further demonstrated that HK intake increased the miR-194 expression in the cortical collecting duct. HK intake decreased the expression of intersectin 1 (ITSN1) which enhanced With-No-Lysine Kinase (WNK)-induced endocytosis of ROMK. Expression of miR-194 mimic decreased luciferase reporter gene activity in HEK293 T cells transfected with ITSN-1–3′UTR containing the complementary seed sequence for miR-194. In contrast, transfection of miR-194 inhibitor increased the luciferase activity. This effect was absent in the cells transfected with mutated 3′UTR of ITSN1 in which the complimentary seed sequence was deleted. Moreover, the inhibition of miR-194 expression increased the protein level of endogenous ITSN1 in HEK293T cells. Expression of miR-194 mimic also decreased the translation of exogenous ITSN1 in the cells transfected with the ITSN1 containing 3′UTR but not with 3′UTR-free ITSN1. Expression of pre-miR-194 increased K currents and ROMK expression in the plasma membrane in ROMK-transfected cells. Coexpression of ITSN1 reversed the stimulatory effect of miR-194 on ROMK channels. This effect was reversed by coexpression of ITSN1. We conclude that miR-194 regulates ROMK channel activity by modulating ITSN1 expression thereby enhancing ITSN1/WNK-dependent endocytosis. It is possible that miR-194 is involved in mediating the effect of a HK intake on ROMK channel activity.


1982 ◽  
Vol 47 (01) ◽  
pp. 022-026 ◽  
Author(s):  
D E MacIntyre ◽  
T J Rink

SummaryThe membrane potential of human platelets, and the role of this potential in platelet aggregation, was assessed using the non-covalent, fluorescent probe DiS-C3-5. High K+ and Gramicidin depolarised the cells, whereas valinomycin in standard (4 mMK+) solution produced a hyperpolarisation. Very small changes in potential were observed when choline Cl replaced NaCl. These findings indicate that platelets possess a relatively K+-permselective membrane. The resting potential calculated from the “valinomycin null point” (the K+ concentration gradient at which valinomycin did not change the potential) was approximately – 60 mV. Other factors that contribute to the platelet membrane potential include a significant Cl− permeability, demonstrated by replacing Cl− with methylsulphate, and an electrogenic Na+ pump, demonstrated using strophanthidin. Little or no change in potential was observed upon addition of ADP, collagen, U44069 or thrombin. Neither strong depolarisation with high K+ or gramicidin nor hyperpolarisation with valinomycin induced platelet aggregation or altered platelet responses to agonists. It is concluded that the information transduction mechanisms involved in platelet activation do not include changes in platelet membrane potential.


2014 ◽  
Vol 306 (12) ◽  
pp. F1507-F1519 ◽  
Author(s):  
María Castañeda-Bueno ◽  
Luz Graciela Cervantes-Perez ◽  
Lorena Rojas-Vega ◽  
Isidora Arroyo-Garza ◽  
Norma Vázquez ◽  
...  

Modulation of Na+-Cl− cotransporter (NCC) activity is essential to adjust K+ excretion in the face of changes in dietary K+ intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K+ diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K+-citrate diets for 4 days. The low-K+ diet decreased and high-K+ diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr44/Thr48/Thr53) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser383/Ser325). The effect of the low-K+ diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K+ diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K+ diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K+-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K+ increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K+ diet.


1984 ◽  
Vol 224 (3) ◽  
pp. 1027-1030 ◽  
Author(s):  
M D Brand ◽  
S M Felber

TMB-8 inhibited respiration of rat thymocytes and rat liver mitochondria, probably by inhibition of NADH dehydrogenase. TMB-8 markedly decreased both the cellular ATP concentration and the mitochondrial membrane potential in situ in thymocytes. These effects occurred at, or well below, the concentrations used in other systems to investigate the role of intracellular calcium pools in signalling events. We conclude that caution should be exercised in the interpretation of the effects of TMB-8.


2013 ◽  
Vol 41 (2) ◽  
pp. 295-314
Author(s):  
Urszula Kruszelnicka

In the years 1977 - 1980, studies were conducted on the effect of sodium used to supplement low (K = 800 mg/5 kg) and high (K = 1400 mg/5 kg) potassium doses on the content of mineral components, their accumulation in the yield and the percentage of their utilization. The study was carried out on root celery - <i>Apium graveolens</i> L. var. <i>rapaceum</i> (Mill.) and stalk celery - <i>Apium graveolens</i> L. var. <i>dulce</i> (Mill.). The results obtained in these experiments point to the following conclusions: it was found that potassium and sodium mutually limit each other's uptake. Sodium was more antagonistic towards the uptake of calcium than was potassium. However, no clearly antagonistic effect of these elements on the uptake of magnesium was determined. The accumulation of potassium and sodium by the experimental plants rose while the percentage of utilization of these elements decreased as their level in the nutrient medium increased. Sodium exerted a more distinct effect on the accumulation and utilization of other mineral elements than did potassium.


1968 ◽  
Vol 52 (1) ◽  
pp. 88-110 ◽  
Author(s):  
Harold Gainer

Potassium contractures were induced in lobster muscle bundles under conditions which produced varying KCl fluxes into the fibers. The presence or absence of chloride fluxes during depolarization by high concentrations of potassium, had no effect on the tensions developed. The curve relating tension to the membrane potential had a typical sigmoid shape with an apparent "threshold" for tension at -60 mv. Soaking the muscles in low (0.1 mM) calcium salines for 30 min completely eliminated the potassium contractures but the caffeine contractures were only slightly reduced under these conditions. The potassium contracture could be completely restored in less than 2 min by return of the calcium ions to the saline. Evidence is presented for independent, superficial, and deep calcium sites; the superficial sites appear to be involved in the coupling mechanisms associated with potassium contractures. These sites are highly selective for Ca++, and attempts to substitute either Cd++, Co++, Mg++, Ba++, or Sr++ for Ca++ were unsuccessful. However, K+ appeared to compete with Ca++ for these sites, and the evoked tension could be reduced by prestimulation of the muscle fibers with high K+ salines. The results of studies on the influx of 45Ca during potassium contractures were compatible with the view of muscle activation by the entry of extracellular calcium.


Sign in / Sign up

Export Citation Format

Share Document