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1.
To the revolution-ellipsoidal and spherical membranous shell (cell mitochondrion) are introduced the equations for the calculation of both the modulus of elasticity (Young's modulus) and the stresses, which exist at the membrane. The existing pressure difference between the inner and outer surface of the membrane is calculated in the dilution of seawater media in the osmotic steady state. The experimental results are obtained by using egg cells of the sea urchin, Strongylocentrotus purpuratus. Up to the specific volume of the egg cell (VE ≈ 35·10-8 cm3) Boyle-van't Hoff's law is valid (defined as the subelastic range) beyond that the elastic stresses exist (elastic range). For the maximum value of the stresses existing at the cell wall one obtains σ ≈ 5.5·106 dyne/cm2 and for the modulus of elasticity E = 1.0·107 dyne/cm2, which is constant when the value of relative strain εν > 15%. The breaking limit by an approximate calculation is σU ≈ 11·106 dyne/cm2. The membrane is assumed to be convoluted and its hypothetical degree of folding was calculated [unk]a = 34%. The results are compared with the values existing in the literature and other types of cells are found to have values of elasticity in the same range as values of the membrane of S. purpuratus. Both compression and cell elastometer methods are criticized and in certain cases results of these methods are considered to belong to the subelastic domain.  相似文献   

2.

Aims

Protein kinase Cα (PKCα) is one of the predominant PKC isoforms that phosphorylate cardiac troponin. PKCα is implicated in heart failure and serves as a potential therapeutic target, however, the exact consequences for contractile function in human myocardium are unclear. This study aimed to investigate the effects of PKCα phosphorylation of cardiac troponin (cTn) on myofilament function in human failing cardiomyocytes and to resolve the potential targets involved.

Methods and Results

Endogenous cTn from permeabilized cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was exchanged (∼69%) with PKCα-treated recombinant human cTn (cTn (DD+PKCα)). This complex has Ser23/24 on cTnI mutated into aspartic acids (D) to rule out in vitro cross-phosphorylation of the PKA sites by PKCα. Isometric force was measured at various [Ca2+] after exchange. The maximal force (Fmax) in the cTn (DD+PKCα) group (17.1±1.9 kN/m2) was significantly reduced compared to the cTn (DD) group (26.1±1.9 kN/m2). Exchange of endogenous cTn with cTn (DD+PKCα) increased Ca2+-sensitivity of force (pCa50 = 5.59±0.02) compared to cTn (DD) (pCa50 = 5.51±0.02). In contrast, subsequent PKCα treatment of the cells exchanged with cTn (DD+PKCα) reduced pCa50 to 5.45±0.02. Two PKCα-phosphorylated residues were identified with mass spectrometry: Ser198 on cTnI and Ser179 on cTnT, although phosphorylation of Ser198 is very low. Using mass spectrometry based-multiple reaction monitoring, the extent of phosphorylation of the cTnI sites was quantified before and after treatment with PKCα and showed the highest phosphorylation increase on Thr143.

Conclusion

PKCα-mediated phosphorylation of the cTn complex decreases Fmax and increases myofilament Ca2+-sensitivity, while subsequent treatment with PKCα in situ decreased myofilament Ca2+-sensitivity. The known PKC sites as well as two sites which have not been previously linked to PKCα are phosphorylated in human cTn complex treated with PKCα with a high degree of specificity for Thr143.  相似文献   

3.
S H White 《Biophysical journal》1970,10(12):1127-1148
A method is described for measuring the specific capacitance (Cm) of lipid bilayer membranes with an estimated experimental error of only 1%. The gross capacitance was measured with an AC Wheatstone bridge and a photographic technique was used to determine the area of thin membrane. The results of measurements on oxidized cholesterol-decane membranes formed in 1 × 10-2 M KCl show that Cm depends upon temperature, voltage, time, and the age of the bulk membrane solutions. For a freshly thinned membrane (from 5 week old solution), Cm increases exponentially from an initial value of 0.432 ±0.021 (SD) μF/cm2 with a time constant of ~15 min. A 100 mv potential applied across the membrane for 10-20 min prior to making measurements eliminated this time dependence and produced final-state membranes. Cm of final-state membranes depends upon applied voltage (Va) and obeys the equation Cm = C0 + βVa2 where Va VDC + VrmsAC. C0 and β depend upon temperature; C0 decreases linearly with temperature while β increases linearly. At 20°C, C0 = 0.559 ±0.01 (SD) μF/cm2 and β = 0.0123 ±0.0036 (SD) (μF/cm2)/(mv2) and at 34°C, C0 = 0.472 ±0.01 and β = 0.0382 ±0.0039. These variations in Cm are interpreted as resulting from thickness changes. The possibility that they result from diffuse layer and/or membrane dielectric phenomena is discussed and found to be unlikely. The results are discussed in terms of membrane stability by constructing hypothetical potential energy vs. thickness curves.  相似文献   

4.
Transmembrane proteins are embedded in cellular membranes of varied lipid composition and geometrical curvature. Here, we studied for the first time the allosteric effect of geometrical membrane curvature on transmembrane protein structure and function. We used single-channel optical analysis of the prototypic transmembrane β-barrel α-hemolysin (α-HL) reconstituted on immobilized single small unilamellar liposomes of different diameter and therefore curvature. Our data demonstrate that physiologically abundant geometrical membrane curvatures can enforce a dramatic allosteric regulation (1000-fold inhibition) of α-HL permeability. High membrane curvatures (1/diameter ∼1/40 nm−1) compressed the effective pore diameter of α-HL from 14.2 ± 0.8 Å to 11.4 ± 0.6 Å. This reduction in effective pore area (∼40%) when combined with the area compressibility of α-HL revealed an effective membrane tension of ∼50 mN/m and a curvature-imposed protein deformation energy of ∼7 kBT. Such substantial energies have been shown to conformationally activate, or unfold, β-barrel and α-helical transmembrane proteins, suggesting that membrane curvature could likely regulate allosterically the structure and function of transmembrane proteins in general.  相似文献   

5.
This paper presents a theoretical analysis of the kinetics of osmotic transport across a semipermeable membrane. There is a thermodynamic connection between the rate of flow under a hydrostatic pressure difference and the rate of flow due to a difference in solute concentration on the two sides. One might therefore attempt to calculate the osmotic transport coefficient by applying Poiseuille's equation to the flow produced by a difference in hydrostatic pressure. Such a procedure is, however, inappropriate if the pores in the membrane are too small to allow molecules to “overtake.” It then becomes necessary to perform a statistical calculation of the transport coefficient, and such a calculation is described in this paper. The resulting expression for the number of solvent molecules passing through a pore per second is J = m D1 δn1/l2 where m is the number of solvent molecules in the pore, l is the length of the pore, D1 is the self-diffusion coefficient of the solute, and δn1 the difference in solvent mole fraction on the two sides of the membrane. This equation is used for estimating the number of pores per unit area of the squid axon membrane; the result is 6 × 109 pores/cm2.  相似文献   

6.
There is growing recognition that lipid heterogeneities in cellular membranes play an important role in the distribution and functionality of membrane proteins. However, the detection and characterization of such heterogeneities at the cellular level remains challenging. Here we report on the poorly understood relationship between lipid bilayer asymmetry and membrane protein sequestering in raft-mimicking model membrane mixtures using a powerful experimental platform comprised of confocal spectroscopy XY-scan and photon-counting histogram analyses. This experimental approach is utilized to probe the domain-specific sequestering and oligomerization state of αvβ3 and α5β1 integrins in bilayers, which contain coexisting liquid-disordered/liquid-ordered (ld/lo) phase regions exclusively in the top leaflet of the bilayer (bottom leaflet contains ld phase). Comparison with previously reported integrin sequestering data in bilayer-spanning lo-ld phase separations demonstrates that bilayer asymmetry has a profound influence on αvβ3 and α5β1 sequestering behavior. For example, both integrins sequester preferentially to the lo phase in asymmetric bilayers, but to the ld phase in their symmetric counterparts. Furthermore, our data show that bilayer asymmetry significantly influences the role of native ligands in integrin sequestering.  相似文献   

7.
Alginate lyases are enzymes that degrade alginate through β-elimination of the glycosidic bond into smaller oligomers. We investigated the alginate lyases from Vibrio splendidus 12B01, a marine bacterioplankton species that can grow on alginate as its sole carbon source. We identified, purified, and characterized four polysaccharide lyase family 7 alginates lyases, AlyA, AlyB, AlyD, and AlyE, from V. splendidus 12B01. The four lyases were found to have optimal activity between pH 7.5 and 8.5 and at 20 to 25°C, consistent with their use in a marine environment. AlyA, AlyB, AlyD, and AlyE were found to exhibit a turnover number (kcat) for alginate of 0.60 ± 0.02 s−1, 3.7 ± 0.3 s−1, 4.5 ± 0.5 s−1, and 7.1 ± 0.2 s−1, respectively. The Km values of AlyA, AlyB, AlyD, and AlyE toward alginate were 36 ± 7 μM, 22 ± 5 μM, 60 ± 2 μM, and 123 ± 6 μM, respectively. AlyA and AlyB were found principally to cleave the β-1,4 bonds between β-d-mannuronate and α-l-guluronate and subunits; AlyD and AlyE were found to principally cleave the α-1,4 bonds involving α-l-guluronate subunits. The four alginate lyases degrade alginate into longer chains of oligomers.  相似文献   

8.
The elastic behavior of the cell wall as a function of the temperature has been studied with particular attention being given to the swelling of egg cells of Strongylocentrotus purpuratus and Crassostrea virginica in different sea water concentrations at different temperatures. It was found that the modulus of elasticity is a nonlinear function of temperature. At about 12-13°C the modulus of elasticity (E) is constant, independent of the stress (σ) and strain (εν) which exist at the cell wall; the membranous material follows Hooke's law, and E ≈ 3 × 107 dyn/cm2 for S. purpuratus and C. virginica. When the temperature is higher or lower than 12-13°C, the modulus of elasticity increases, and the membranous material does not follow Hooke's law, but is almost directly proportional to the stresses existing at the cell wall. On increasing the stress, the function Eσ = E(σ) approaches saturation. The corresponding stress-strain diagrams, σ = σ(εν), and the graphs, Eσ = E(σ) and Eσ = E(t) are given. The cyto-elastic phenomena at the membrane are discussed.  相似文献   

9.
A new oriented method using a diazonium salt reaction was developed for linking β 2-adrenoceptor (β 2-AR) on the surface of macroporous silica gel. Stationary phase containing the immobilised receptor was used to investigate the interaction between β 2-AR and ephedrine plus pseudoephedrine by zonal elution. The isotherms of the two drugs best fit the Langmuir model. Only one type of binding site was found for ephedrine and pseudoephedrine targeting β 2-AR. At 37 °C, the association constants during the binding were (5.94±0.05)×103/M for ephedrine and (3.80±0.02) ×103/M for pseudoephedrine, with the binding sites of (8.92±0.06) ×10−4 M. Thermodynamic studies showed that the binding of the two compounds to β 2-AR was a spontaneous reaction with exothermal processes. The ΔGθ, ΔHθ and ΔSθ for the interaction between ephedrine and β 2-AR were −(22.33±0.04) kJ/mol, −(6.51±0.69) kJ/mol and 50.94±0.31 J/mol·K, respectively. For the binding of pseudoephedrine to the receptor, these values were −(21.17±0.02) kJ/mol, −(7.48±0.56) kJ/mol and 44.13±0.01 J/mol·K. Electrostatic interaction proved to be the driving force during the binding of the two drugs to β 2-AR. The proposed immobilised method will have great potential for attaching protein to solid substrates and realizing the interactions between proteins and drugs.  相似文献   

10.
The synthesis of α-tocopherol from 2,3-dimethylphytylquinol and S-adenosyl-l-methionine was achieved using Capsicum annuum fruit chromoplasts. The enzymes involved in the cyclization (2,3-dimethyl-phytylquinol cyclase) and methylation (S-adenosyl methionine:γ-tocopherol methyl-transferase) are both localized in the chromoplast membrane fraction (envelopes and/or a-chlorophyll lamellae), in contrast to the stroma fraction.  相似文献   

11.
In this work, we utilize micropipette aspiration and fluorescence imaging to examine the material properties of lipid vesicles made from mixtures of palmitoyloleoylphosphocholine (POPC) and dipalmitoylphosphatidylcholine (DPPC). At elevated temperatures/low DPPC fractions, these lipids are in a miscible liquid crystalline (Lα) state, whereas at lower temperatures/higher DPPC fractions they phase-separate into Lα and gel phases. We show that the elastic modulus, K, and critical tension, τc, of Lα vesicles are independent of DPPC fraction. However, as the sample temperature is increased from 15°C to 45°C, we measure decreases in both K and τc of 20% and 50%, respectively. The elasticity change is likely driven by a change in interfacial tension. We describe the reduction in critical tension using a simple model of thermally activated membrane pores. Vesicles with two-phase coexistence exhibit material properties that differ from Lα vesicles including critical tensions that are 20–40% lower. Fluorescence imaging of phase coexistent POPC/DPPC vesicles shows that the DPPC-rich domains exist in an extended network structure that exhibits characteristics of a solid. This gel network explains many of the unusual material properties of two-phase membranes.  相似文献   

12.
The cytoplasm and the vacuole were isolated from internodal cells of Chara corallina by using the intracellular perfusion technique, and their buffer capacities (βi) were determined from the titration curves. The pH of the isolated vacuolar sap was 5.19 ± 0.029 (mean ± standard error). At this pH, βi was minimal and amounted to 0.933 ± 0.11 millimoles H+/pH unit/liter vacuolar sap. The pH of isolated cytoplasm was 7.22 ± 0.028. βi was minimal in this pH region and amounted to 14.2 ± 0.80 millimoles H+/pH unit/liter cytoplasm. When 1% (volume/volume) Triton X-100 was added to the cytoplasmic solution to permeabilize the subcellular organelles, the cytoplasmic pH increased to 7.32 ± 0.026, where βi was 20.35 ± 2.66 millimoles H+/pH unit/liter cytoplasm. This shows that alkaline subcellular compartments exist in the cytoplasm and also that the cytoplasmic pH before adding Triton X-100 may represent the cytosolic pH. These data indicate that the pH values of the cytoplasm and the vacuole are regulated at the values where the βi values are minimal. This suggests that ATP- and inorganic pyrophosphate-dependent H+ pumps in the plasma membrane and the tonoplast could efficiently regulate the pH of both cytoplasm and vacuole in Chara internodal cells.  相似文献   

13.
Oncogenic mutations in PIK3CA lead to an increase in intrinsic phosphoinositide kinase activity, but it is thought that increased access of PI3Kα (phosphoinositide 3-kinase α) to its PM (plasma membrane) localized substrate is also required for increased levels of downstream PIP3/Akt [phosphoinositide-3,4,5-trisphosphate/also called PKB (protein kinase B)] signalling. We have studied the subcellular localization of wild-type and the two most common oncogenic mutants of PI3Kα in cells maintained in growth media, and starved or stimulated cells using a novel method in which PI3Kα is pre-formed as a 1:1 p110α:p85α complex in vitro then introduced into live cells by microinjection. Oncogenic E545K and H1047R mutants did not constitutively interact with membrane lipids in vitro or in cells maintained in 10% (v/v) FBS. Following stimulation of RTKs (receptor tyrosine kinases), microinjected PI3Kα was recruited to the PM, but oncogenic forms of PI3Kα were not recruited to the PM to a greater extent and did not reside at the PM longer than the wild-type PI3Kα. Instead, the E545K mutant specifically bound activated Cdc42 in vitro and microinjection of E545K was associated with the formation of cellular protrusions, providing some preliminary evidence that changes in protein–protein interactions may play a role in the oncogenicity of the E545K mutant in addition to the well-known changes in lipid kinase activity.  相似文献   

14.

Background

To make a radiobiological comparison, for high risk prostate cancer (T3a, PSA > 20 ng/ml or Gleason > 7) of two radiotherapy treatment techniques. One technique consists of a treatment in three phases of the pelvic nodes, vesicles and prostate using a conventional fractionation scheme of 2 Gy/fraction (SIMRT). The other technique consists of a treatment in two phases that gives simultaneously different dose levels in each phase, 2 Gy/fraction, 2.25 Gy/fraction and 2.5 Gy/fraction to the pelvic nodes, vesicles and prostate, respectively (SIBIMRT).

Materials and methods

The equivalent dose at fractionation of 2 Gy (EQD2), calculated using the linear quadratic model with α/βprostate = 1.5 Gy, was the same for both treatment strategies. For comparison the parameters employed were D95, mean dose and Tumour Control Probabilities for prostate PTV and D15, D25, D35, D50, mean dose and Normal Tissue Complication Probabilities for the rectum and bladder, with physical doses converted to EQD2. Parameters were obtained for α/βprostate = 1.5, 3 and 10 Gy and for α/βoar = 1, 2, 3, 4, 6 and 8.

Results

For prostate PTV, both treatment strategies are equivalent for α/βprostate = 1.5 Gy but for higher α/βprostate, EQD2 and TCP, decrease for the SIBIMRT technique. For the rectum and bladder when α/βoar ≤ 2 Gy, EQD2 and NTCP are lower for the SIMRT technique or equal in both techniques. For α/βoar ≥ 2–3 Gy, EQD2 and NTCP increase for the SIMRT treatment.

Conclusions

A comparison between two radiotherapy techniques is presented. The SIBIMRT technique reduces EQD2 and NTCP for α/βoar from 2 to 8 Gy.  相似文献   

15.
The State of Water in Human and Dog Red Cell Membranes   总被引:8,自引:8,他引:0  
The apparent activation energy for the water diffusion permeability coefficient, Pd, across the red cell membrane has been found to be 4.9 ± 0.3 kcal/mole in the dog and 6.0 ± 0.2 kcal/mole in the human being over the temperature range, 7° to 37°C. The apparent activation energy for the hydraulic conductivity, Lp, in dog red cells has been found to be 3.7 ± 0.4 kcal/mole and in human red cells, 3.3 ± 0.4 kcal/mole over the same temperature range. The product of Lp and the bulk viscosity of water, η, was independent of temperature for both dog and man which indicates that the geometry of the red cell membrane is not temperature-sensitive over our experimental temperature range in either species. In the case of the dog, the apparent activation energy for diffusion is the same as that for self-diffusion of water, 4.6–4.8 kcal/mole, which indicates that the process of water diffusion across the dog red cell membrane is the same as that in free solution. The slightly, but significantly, higher activation energy for water diffusion in human red cells is consonant with water-membrane interaction in the narrower equivalent pores characteristic of these cells. The observation that the apparent activation energy for hydraulic conductivity is less than that for water diffusion across the red cell membrane is characteristic of viscous flow and suggests that the flow of water across the membranes of these red cells under an osmotic pressure gradient is a viscous process.  相似文献   

16.
Water movement across plant tissues occurs along two paths: from cell-to-cell and in the apoplasm. We examined the contribution of these two paths to the kinetics of water transport across the parenchymatous midrib tissue of the maize (Zea mays L.) leaf. Water relations parameters (hydraulic conductivity, Lp; cell elastic coefficient, ε; half-time of water exchange for individual cells, T½) of individual parenchyma cells determined with the pressure probe varied in different regions of the midrib. In the adaxial region, Lp = (0.3 ± 0.3)·10−5 centimeters per second per bar, ε = 103 ± 72 bar, and T½ = 7.9 ± 4.8 seconds (n = seven cells); whereas, in the abaxial region, Lp = (2.5 ± 0.9)·10−5 centimeters per second per bar, ε = 41 ± 9 bar, and T½ = 1.3 ± 0.5 seconds (n = 7). This zonal variation in Lp, ε, and T½ indicates that tissue inhomogeneities exist for these parameters and could have an effect on the kinetics of water transport across the tissue.

The diffusivity of the tissue to water (Dt) obtained from the sorption kinetics of rehydrating tissue was Dt = (1.1 ± 0.4)·10−6 square centimeters per second (n = 6). The diffusivity of the cell-to-cell path (Dc) calculated from pressure probe data ranged from Dc = 0.4·10−6 square centimeters per second in the adaxial region to Dc = 6.1·10−6 square centimeters per second in the abaxial region of the tissue. Dt Dc suggests substantial cell-to-cell transport of water occurred during rehydration. However, the tissue diffusivity calculated from the kinetics of pressure-propagation across the tissue (Dt′) was Dt′ = (33.1 ± 8.0)·10−6 square centimeters per second (n = 8) and more than 1 order of magnitude larger than Dt. Also, the hydraulic conductance of the midrib tissue (Lpm per square centimeter of surface) estimated from pressure-induced flows across several parenchyma cell layers was Lpm = (8.9 ± 5.6)·10−5 centimeters per second per bar (n = 5) and much larger than Lp.

These results indicate that the preferential path for water transport across the midrib tissue depends on the nature of the driving forces present within the tissue. Under osmotic conditions, the cell-to-cell path dominates, whereas under hydrostatic conditions water moves primarily in the apoplasm.

  相似文献   

17.
The metabolism of protocatechuate by Pseudomonas testosteroni   总被引:5,自引:5,他引:0  
1. Protocatechuate 4,5-oxygenase, purified 21-fold from extracts of Pseudomonas testosteroni, was examined in the ultracentrifuge and assigned a mol.wt. of about 140000. 2. When diluted, the enzyme rapidly lost activity during catalysis. Inactivation was partially prevented by l-cysteine. 3. With a saturating concentration of protocatechuate (1·36mm), Km for oxygen was 0·303mm. This value is greater than the concentration of oxygen in water saturated with air at 20°. 4. Cell extracts converted protocatechuate into γ-carboxy-γ-hydroxy-α-oxovalerate, which was isolated as its lactone. 5. γ-Carboxy-γ-hydroxy-α-oxovalerate pyruvate-lyase activity was stimulated by Mg2+ ions and mercaptoethanol. Cells grown with p-hydroxybenzoate as carbon source contained higher concentrations of this enzyme than those grown with succinate.  相似文献   

18.
Tension and curvature of the sarcolemmal tube of the frog muscle fiber were measured at different extensions and were used to calculate the anisotropic elastic properties of the sarcolemma. A model was derived to obtain the four parameters of the elasticity matrix of the sarcolemma. Sarcolemmal thickness was taken as 0.1 μm. Over the range of reversible sarcolemmal tube extension, the longitudinal elastic modulus EL = 6.3 × 107 dyn/cm2, the circumferential modulus Ec = 0.88 × 107 dyn/cm2, the longitudinal Poisson's ratio σL = 1.2, and the circumferential Poisson's ratio σc = 0.18. At tubular rest length EL = 1.2 × 107 dyn/cm2. The sarcolemma is less extensible in the longitudinal direction along the fiber axis than in the circumferential direction. It can be extended reversibly to 48% of its rest length, equivalent to extending the intact fiber from a sarcomere length of 3 μm to about 4.5 μm. The sarcolemma does not contribute to intact fiber tension at fiber sarcomere lengths <3 μm, and between 3 and 4 μm its contribution is about 20%. It also exerts a pressure on the myoplasm, which can be calculated by means of the model. The longitudinal elastic modulus of the whole fiber is 1 × 105 dyn/cm2 at a sarcomere length of 2.33 μm.  相似文献   

19.
1. The reaction between β-bromopyruvic acid and SH groups of cysteine residues in reduced ribonuclease and in some other polypeptides was investigated. 2. One molecule of the acid was found to be necessary to block one SH group in reduced ribonuclease. The stoicheiometry of the interaction and the spectral characteristics of the compound formed suggested that the product is and S-oxalomethyl (R·S·CH2·CO·CO2H) derivative of reduced ribonuclease. 3. Digestion of reduced S-oxalomethylated ribonuclease by trypsin or chymotrypsin induced changes in the spectrum that could be attributed to the liberation of the α-amino group of S-oxalomethylated cysteine residues from peptide bonds. The spectral changes that accompanied the hydrolysis of specific peptide bonds in reduced S-oxalomethylated ribonuclease and S-oxalomethylated co-poly(l-Lys,l-CySH) allowed the kinetics of the digestion to be followed. 4. Possible applications of the spectrophotometric method in the study of protein structure are discussed.  相似文献   

20.
Dephosphorylation of important myocardial proteins is regulated by protein phosphatase 2A (PP2A), representing a heterotrimer that is comprised of catalytic, scaffolding, and regulatory (B) subunits. There is a multitude of B subunit family members directing the PP2A holoenzyme to different myocellular compartments. To gain a better understanding of how these B subunits contribute to the regulation of cardiac performance, we generated transgenic (TG) mice with cardiomyocyte-directed overexpression of B56α, a phosphoprotein of the PP2A-B56 family. The 2-fold overexpression of B56α was associated with an enhanced PP2A activity that was localized mainly in the cytoplasm and myofilament fraction. Contractility was enhanced both at the whole heart level and in isolated cardiomyocytes of TG compared with WT mice. However, peak amplitude of [Ca]i did not differ between TG and WT cardiomyocytes. The basal phosphorylation of cardiac troponin inhibitor (cTnI) and the myosin-binding protein C was reduced by 26 and 35%, respectively, in TG compared with WT hearts. The stimulation of β-adrenergic receptors by isoproterenol (ISO) resulted in an impaired contractile response of TG hearts. At a depolarizing potential of −5 mV, the ICa,L current density was decreased by 28% after administration of ISO in TG cardiomyocytes. In addition, the ISO-stimulated phosphorylation of phospholamban at Ser16 was reduced by 27% in TG hearts. Thus, the increased PP2A-B56α activity in TG hearts is localized to specific subcellular sites leading to the dephosphorylation of important contractile proteins. This may result in higher myofilament Ca2+ sensitivity and increased basal contractility in TG hearts. These effects were reversed by β-adrenergic stimulation.  相似文献   

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