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31.
Starkus JG Varga Z Schönherr R Heinemann SH 《Pflügers Archiv : European journal of physiology》2003,447(1):44-54
Potassium channels are regulated by protons in various ways and, in most cases, acidification results in potassium current reduction. To elucidate the mechanisms of proton-channel interactions we investigated N-terminally truncated Shaker potassium channels (Kv1 channels) expressed in Xenopus oocytes, varying pH at the intracellular and the extracellular face of the membrane. Intracellular acidification resulted in rapid and reversible channel block. The block was half-maximal at pH 6.48, thus even physiological excursions of intracellular pH will have an impact on K+ current. The block displayed only very weak voltage dependence and C-type inactivation and activation were not affected. Extracellular acidification (up to pH 4) did not block the channel, indicating that protons are effectively excluded from the selectivity filter. Channel current, however, was reduced greatly due to marked acceleration of C-type inactivation at low pH. In contrast, inactivation was not affected in the T449V mutant channel, in which C-type inactivation is impaired. The pH effect on inactivation of the wild-type channel had an apparent pK of 4.7, suggesting that protonation of extracellular acidic residues in Kv channels makes them subject to pH regulation. 相似文献
32.
Eva Díez‐Pea Isabel Quijada‐Garrido Jos Manuel Barrales‐Rienda Ingo Schnell Hans Wolfgang Spiess 《Macromolecular chemistry and physics.》2004,205(4):430-437
Summary: The nature of the pH dependent collapse of poly(methacrylic acid) (PMAA) hydrogels is investigated using recent 1H solid‐state NMR methods. In aqueous solution, PMAA changes from an expanded conformation at high pHs to a compact contracted form at low pHs, where hydrogen bonds play a central role. In solid‐state 1H NMR spectra, recorded under fast magic angle spinning (MAS), dried PMAA samples previously collapsed at low pHs show characteristic signals in the spectral region of the carboxylic acid protons. With the aid of 2D 1H‐1H double‐quantum (DQ) MAS NMR spectra, three signals can be distinguished at 8, 10.5 and 12.5 ppm, which are attributed to free carboxylic groups and two different types of hydrogen bonded forms, respectively. The 12.5 ppm signal arises from the hydrogen bond with the shortest H? H distance, corresponding to the form that is most stable with respect to increasing temperature and pH. The weaker hydrogen‐bonded form (with a signal at 10.5 ppm) requires a slightly lower pH, while the free acid signal (at 8 ppm) emerges under the most acidic medium. Moreover, the stabilities of the hydrogen‐bonded carboxylic acid dimers can be inferred from the proton‐proton distances within the dimers, i.e. (275 ± 5) pm and (295 ± 15) pm for the protons at 12.5 and 10.5 ppm, respectively, which are determined by means of DQ MAS sideband patterns. Both the stability of the hydrogen bonds and the acidity of the protons may be related to the stereochemistry and the conformation of the PMAA chains.
33.
Intracellular pH changes affect excitation-contraction coupling in skeletal, and cardiac muscles. However the proton implication
in modulating the sarcoplasmic reticulum Ca2+ release channel activity has never been visualized at single channel level. A large conducting Ca2+ release pathway has previously been characterized after incorporation of skeletal and cardiac sarcoplasmic reticulum vesicles
into planar lipid bilayers. This channel has been activated by micromolar and millimolar concentrations of Ca2+ and ATP, respectively. The pH was independently varied on each side of the channels. Acidification of the cis-chamber (7.4
to 6.6) induced a modification of the gating behaviour, resulting in a decrease of the open probability. This effect was completely
reversible. On the other hand, acidification of the trans-chamber (7.4 to 6.8) induced a reduction of the unitary conductance
of the sarcoplasmic reticulum Ca2+ release channel. 相似文献
34.
Jiří Bártek Vladimir Viklický František Franěk Pavla Angelisová Pavel Dráber Taťána Jarošíková Miloš Němec Hana Verlová 《Immunology letters》1982,4(5):231-235
Five stable hybridoma lines were prepared using the myeloma cell line P3-X63-Ag.653 and spleen cells of mice hyperimmunized by pig transferrin. All hybridomas grew well in mouse peritoneal cavity and produced antibodies of the IgG1 subclass. Antibody preparations obtained from ascitic fluids tested for their capacity of antigen precipitation. No precipitation was obtained with single antibodies and with pairs of antibodies. Three out of 10 possible triads gave clear and sharp precipitation zones and rings in immunodiffusion tests performed in agar gel. All 5 antibodies were shown by quantitative enzyme-immunoassay to be specific for pig transferrin: no cross-reaction was obtained with mouse, human, horse and sheep transferrins. 相似文献
35.
Yoshitaka Saito Terutaka Ozawa Akinori Nishiyama 《Pflügers Archiv : European journal of physiology》1990,417(4):382-390
Kinetic properties of the Na+-H+ antiport in the acinar cells of the isolated, superfused mouse lacrimal gland were studied by measuring intracellular pH (pHi) and Na+ activity (aNai) with the aid of double-barreled H+- and Na+-selective microelectrodes, respectively. Bicarbonate-free solutions were used throughout. Under untreated control conditions, pHi was 7.12±0.01 and aNai was 6.7±0.6 mmol/l. The cells were acid-loaded by exposure to an NH
4
+
solution followed by an Na+-free N-methyl-d-glucamine (NMDG+) solution. Intracellular Na+ and H+ concentrations were manipulated by changing the duration of exposure to the above solutions. Subsequent addition of the standard Na+ solution rapidly increased pHi. This Na+-induced increase in pHi was almost completely inhibited by 0.5 mmol/l amiloride and was associated with a rapid, amiloride-sensitive increase in aNai. The rate of pHi recovery induced by the standard Na+ solution increased in a saturable manner as pHi decreased, and was negligible at pHi 7.2–7.3, indicating an inactivation of the Na+-H+ antiport. The apparent K
m for intracellular H+ concentration was 105 nmol/l (pH 6.98). The rate of acid extrusion from the acid-loaded cells increased proportionally to the increase in extracellular pH. Depletion of aNai to less than 1 mmol/l by prolonged exposure to NMDG+ solution significantly increased the rate of Na+-dependent acid extrusion. The rate of acid extrusion increased as the extracellular Na+ concentration increased following Michaelis-Menten kinetics (V
max was 0.55 pH/min and the apparent K
m was 75 mmol/l at pHi 6.88). The results clearly showed that the Na+-H+ antiport activity is dependent on the chemical potential gradient of both Na+ and H+ ions across the basolateral membrane, and that the antiporter is asymmetric with respect to the substrate affinity of the transport site. The data agree with the current model of activation and inactivation of the antiporter by an intracellular site through changes in the intracellular Na+ and H+ concentrations. 相似文献
36.
R. Fuchs T. Thalhammer M. Peterlik J. Graf 《Pflügers Archiv : European journal of physiology》1986,406(4):430-432
Mechanisms of Na+–H+ exchange in the hepatocyte were studied utilizing isolated basolateral membrane vesicles prepared by two different methods: Evidence was obtained for the existence of molecular coupling of Na+ and H+ fluxes (Na+/H+-antiport) which exhibits saturation kinetics (Km 7 mmol/l Na+) and is inhibited by amiloride (1.0 mmol/l). Although the two membrane preparations showed differences with respect to ionic permeabilities, our data suggest that a relatively high H+ conductance exists in the basolateral plasma membrane. Hence, electrical coupling of conductive H+ and Na+ fluxes in the opposite direction could contribute to net Na+–H+ exchange across the basolateral hepatocyte plasma membrane. 相似文献
37.
The response of isolated brain vessels to various pH levels or carbon dioxide tensions was analyzed. Reduction of the pH induced a slight relaxation of the vessel, whereas an increase in the pH produced a slight contraction. These effects were markedly exaggerated when the alpha-adrenergic receptors in the vascular wall were activated by noradrenaline. During these conditions the contractile response to noradrenaline was reduced by about 40 per cent at a pH of 7.01, while, on the other hand, the response was enhanced 3-fold at a pH of 7.80. Variations in carbon dioxide tension of the buffer solution between 16 mmHg and 64 mmHg produced no consistent change, provided the pH remained constant. The results indicate that an interaction between the perivascular pH and the adrenergic alpha-receptor mediated contraction in brain vessels may occur. 相似文献
38.
D. Willoughby Roger C. Thomas Christof J. Schwiening 《Pflügers Archiv : European journal of physiology》1998,436(4):615-622
We have evaluated the pyrene-based ratiometric fluorescent dye, 8-hydroxypyrene-1,3,6-trisulphonic acid (HPTS), by using
it in conjunction with glass pH-sensitive microelectrodes to measure intracellular pH (pHi) in voltage-clamped snail neurones. Intracellular acidification with propionic acid, and alkalinization following the activation
of H+ channels allowed the calibration of the dye to be compared with that of the pH microelectrode over the pH range 6.50–7.50.
HPTS calibrated in vitro and glass pH-sensitive microelectrodes produced similar absolute resting pHi values, 7.16±0.05 (n=10) and 7.17±0.06 (n=9) respectively in nominally CO2/HCO3
–-free saline. At both extremes of the pH range there were small discrepancies. At acidic pHi, 6.87±0.09 (n=5), the intracellular HPTS measurement differed by –0.08±0.03 pH units from the pH-sensitive microelectrode measurement.
At alkaline pHi,7.32±0.10 (n=5), HPTS measurements produced pH values that differed by +0.07±0.04 pH units from those of the pH-sensitive microelectrode.
Some of the discrepancy could be accounted for by the slow response of the recessed-tip pH-sensitive microelectrode (time
constant 77±15 s, n=3). Further experiments showed that HPTS, used at an intracellular concentration of 200 μM to 2 mM, did not block activity-dependent
pHi changes. The intracellular HPTS concentration was calculated by measurement of intracellular chloride during a series of
HPTS-KCl injections. Comparison of HPTS with 2′,7′-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF), at the same concentration,
showed that HPTS produces a larger change in ratio over the pH range 6.00–8.00.
Received: 19 February 1998 / Received after revision and accepted: 22 April 1998 相似文献
39.
Coping strategies and anxiety responding of dental patients were studied in order to test the generalizability of previous findings based on volunteer blood donors. State and trait coping measures were administered once, and a process coping scale was administered at three points throughout treatment. Self-report, behavioral observation, and psychophysiological measures of anxiety were sampled for the same periods as process coping. Findings included the replication of a negative relationship between avoidant coping and patient anxiety ratings. Fluctuations in coping were evident across periods, and impact of situational demands and constraints was introduced as an explanation for these variations. A method for direct assessment of coping consistency was introduced. On the basis of the replicable associations with anxiety measures, the ability to detect changes in coping within a situation, and the ability to provide direct evidence of coping consistency, the use of process methodology for coping assessment is encouraged.This research was conducted while the first author was supported by funding from the Medical Research Council of Canada.Portions of this research were presented at the annual convention of the Society of Behavioral Medicine, Philadelphia, 1984. 相似文献
40.
Paredes AM Ferreira D Horton M Saad A Tsuruta H Johnston R Klimstra W Ryman K Hernandez R Chiu W Brown DT 《Virology》2004,324(2):373-386
Alphaviruses have the ability to induce cell-cell fusion after exposure to acid pH. This observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid pH after incorporation into a cell endosome. We have investigated the requirements for the induction of virus-mediated, low pH-induced cell-cell fusion and cell-virus fusion. We have correlated the pH requirements for this process to structural changes they produce in the virus by electron cryo-microscopy. We found that exposure to acid pH was required to establish conditions for membrane fusion but that membrane fusion did not occur until return to neutral pH. Electron cryo-microscopy revealed dramatic changes in the structure of the virion as it was moved to acid pH and then returned to neutral pH. None of these treatments resulted in the disassembly of the virus protein icosahedral shell that is a requisite for the process of virus membrane-cell membrane fusion. The appearance of a prominent protruding structure upon exposure to acid pH and its disappearance upon return to neutral pH suggested that the production of a "pore"-like structure at the fivefold axis may facilitate cell penetration as has been proposed for polio (J. Virol. 74 (2000) 1342) and human rhino virus (Mol. Cell 10 (2002) 317). This transient structural change also provided an explanation for how membrane fusion occurs after return to neutral pH. Examination of virus-cell complexes at neutral pH supported the contention that infection occurs at the cell surface at neutral pH by the production of a virus structure that breaches the plasma membrane bilayer. These data suggest an alternative route of infection for Sindbis virus that occurs by a process that does not involve membrane fusion and does not require disassembly of the virus protein shell. 相似文献