scholarly journals Slow diffusion of K+ in the T tubules of rat cardiomyocytes

2006 ◽  
Vol 101 (4) ◽  
pp. 1170-1176 ◽  
Author(s):  
Fredrik Swift ◽  
Tævje A. Strømme ◽  
Bjørn Amundsen ◽  
Ole M. Sejersted ◽  
Ivar Sjaastad
Keyword(s):  
Diffusion Rate ◽  
Osmotic Shock ◽  
Surface Membrane ◽  
Current Control ◽  
Rat Cardiomyocytes ◽  
Steady State Current ◽  
Cardiomyocyte Contractility ◽  
T Tubules ◽  
The Difference ◽  
The Times

Cardiomyocyte contractility is regulated by the extracellular K+ concentration ([K+]o). Potassium dynamics in the T tubules during the excitation-contraction cycle depends on the diffusion rate of K+, but this rate is not known. Detubulation of rat cardiomyocytes was induced by osmotic shock using formamide, which separated the surface membrane from the T tubules. Changes in current and membrane potential in voltage-clamped (−80 mV) and current-clamped control and detubulated cardiomyocytes were compared during rapid switches between 5.4 and 8.1 mM [K+]o, and the results were simulated in a mathematical model. In the voltage-clamp experiments, the current changed significantly slower in control than in detubulated cardiomyocytes during the switch from 5.4 to 8.1 mM [K+]o, as indicated by the times to achieve 25, 50, 90, and 95% of the new steady-state current [control (ms) t25 = 98 ± 12, t50 = 206 ± 20, t90 = 570 ± 72, t95 = 666 ± 92; detubulated t25 = 61 ± 11, t50 = 142 ± 17, t90 = 352 ± 52, t95 = 420 ± 69]. These time points were not significantly different either during the 8.1 to 5.4 mM [K+]o switch or in current-clamped cardiomyocytes switching from 5.4 to 8.1 mM [K+]o. Mathematical simulation of the difference current between control and detubulated cardiomyocytes gave a t-tubular diffusion rate for K+ of ∼85 μm2/s. We conclude that the diffusion of K+ in the T tubules is so slow that they constitute a functional compartment. This might play a key role in local regulation of the action potential, and thus in the regulation of cardiomyocyte contractility.

Excitation-contraction coupling in rat ventricular myocytes after formamide-induced detubulation

1999 ◽  
Vol 277 (2) ◽  
pp. H603-H609 ◽  
Author(s):  
Makoto Kawai ◽  
Munir Hussain ◽  
Clive H. Orchard
Keyword(s):  
Ventricular Myocytes ◽  
Osmotic Shock ◽  
Surface Membrane ◽  
Cardiac Cells ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Simultaneous Measurements ◽  
T Tubules

Formamide-induced osmotic shock has been used to detubulate isolated adult rat ventricular myocytes (i.e., disrupt the surface membrane-T tubule junction). Cell volume, calculated from cell length and width, rapidly decreased and increased upon application and removal of formamide, respectively. After treatment with formamide, membrane capacitance decreased by 26.4% (from 199.4 ± 18.7 pF in control cells to 146.7 ± 6.4 pF in formamide-treated cells; n = 13, P < 0.05). However, the amplitude of the L-type Ca2+ current ( I Ca) decreased by a greater extent (from 0.75 ± 0.14 to 0.18 ± 0.03 nA; n = 5, P < 0.05) so that the density of I Ca decreased by 74.5%. Simultaneous measurements of I Ca and Ca2+ transients (monitored using fura 2) showed that both decreased rapidly upon removal of formamide. However, the Ca2+ content of the sarcoplasmic reticulum showed little change. Cross-striations, visualized with the fluorescent dye di-8-aminonaphthylethenylpyridinium, were sparse or absent in cells that had been treated with formamide, suggesting that formamide can successfully detubulate cardiac cells and that I Ca is concentrated in the T tubules, which therefore play an important role in excitation-contraction coupling.

Inductor Saturation Compensation in Three-Phase Three-Wire Voltage-Source Converters via Inverse System Dynamics-I

2020 ◽  
Author(s):  
Ziya Özkan ◽  
Ahmet Masum Hava
Keyword(s):  
Dynamic Model ◽  
Dynamic Performance ◽  
Current Control ◽  
Inverse System ◽  
Voltage Source ◽  
Voltage Source Converter ◽  
Two Phase ◽  
Inverse Dynamic ◽  
Three Phase ◽  
Steady State Current

In three-phase three-wire (3P3W) voltage-source converter (VSC) systems, utilization of filter inductors with deep saturation characteristics is often advantageous due to the improved size, cost, and efficiency. However, with the use of conventional synchronous frame current control (CSCC) methods, the inductor saturation results in significant dynamic performance loss and poor steady-state current waveform quality. This paper proposes an inverse dynamic model based compensation (IDMBC) method to overcome these performance issues. Accordingly, a review of inductor saturation and core materials is performed, and the motivation on the use of saturable inductors is clarified. Then, two-phase exact modelling of the 3P3W VSC control system is obtained and the drawbacks of CSCC have been demonstrated analytically. Based on the exact modelling, the inverse system dynamic model of the nonlinear system is obtained and employed such that the nonlinear plant is converted to a fictitious linear inductor system for linear current regulators to perform satisfactorily.

The Magnetic Anisotropy of Stretched Rubber as a Function of the Tension to Which It Is Subjected

1945 ◽  
Vol 18 (1) ◽  
pp. 8-9 ◽  
Author(s):  
Eugénie Cotton-Feytis
Keyword(s):  
Magnetic Field ◽  
Magnetic Anisotropy ◽  
Uniaxial Crystal ◽  
Horizontal Magnetic Field ◽  
First Approximation ◽  
The Difference ◽  
The Times ◽  
Angular Displacements ◽  
The Magnetic Field ◽  
Oscillation Method

Abstract From the standpoint of its magnetic anisotropy, stretched rubber is comparable in a first approximation to a uniaxial crystal, in which the direction of the axis is the same as the direction of elongation. It is possible to measure this anisotropy by means of the oscillation method used by Krishnan, Guha and Banerjee in studying crystals. The sample to be examined is suspended in a uniform horizontal magnetic field in such a manner that its axis is horizontal. It is then so arranged that the torsion of the suspension wire is zero when the rubber sample is in a position of equilibrium in the field. The times of oscillation T′ and T for very small angular displacements around this position, in the presence and then in the absence of the magnetic field, are then recorded. In this way the difference between the specific susceptibilities in the direction of the axis and in the horizontal direction perpendicular to the axis is calculated by application of the equation:

scholarly journals Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

2009 ◽  
Vol 297 (2) ◽  
pp. H718-H725 ◽  
Author(s):  
Richard A. Fenton ◽  
Satoshi Komatsu ◽  
Mitsuo Ikebe ◽  
Lynne G. Shea ◽  
James G. Dobson
Keyword(s):  
Confocal Microscopy ◽  
Phospholipase C ◽  
Adrenergic Agonist ◽  
Rat Cardiomyocytes ◽  
Scanning Confocal Microscopy ◽  
Adult Rat ◽  
Sds Page ◽  
T Tubules ◽  
Isolated Rat ◽  
Stimulation Of

Adenosine protects the heart from adrenergic overstimulation. This adenoprotection includes the direct anti-adrenergic action via adenosine A1 receptors (A1R) on the adrenergic signaling pathway. An indirect A1R-induced attenuation of adrenergic responsiveness involves the translocation of PKC-ε to t-tubules and Z-line of cardiomyocytes. We investigated with sarcomere imaging, immunocytochemistry imaging, and coimmunoprecipitation (co-IP) whether A1R activation of PKC-ε induces the kinase translocation to receptor for activated C kinase 2 (RACK2) in isolated rat and mouse hearts and whether phospholipase C (PLC) is involved. Rat cardiomyocytes were treated with the A1R agonist chlorocyclopentyladenosine (CCPA) and exposed to primary PKC-ε and RACK2 antibodies with secondaries conjugated to Cy3 and Cy5 (indodicarbocyanine), respectively. Scanning confocal microscopy showed that CCPA caused PKC-ε to reversibly colocalize with RACK2 within 3 min. Additionally, rat and mouse hearts were perfused and stimulated with CCPA or phenylisopropyladenosine to activate A1R, or with phorbol 12-myristate 13-acetate to activate PKC. RACK2 was immunoprecipitated from heart extracts and resolved with SDS-PAGE. Western blotting showed that CCPA, phenylisopropyladenosine, and phorbol 12-myristate 13-acetate in the rat heart increased the PKC-ε co-IP with RACK2 by 186, 49, and >1,000%, respectively. The A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine prevented the CCPA-induced co-IP with RACK2. In mouse hearts, CCPA increased the co-IP of PKC-ε with RACK2 by 61%. With rat cardiomyocytes, the β-adrenergic agonist isoproterenol increased sarcomere shortening by 177%. CCPA reduced this response by 47%, an action inhibited by the PLC inhibitor U-73122 and 8-cyclopentyl-1,3-dipropylxanthine. In conclusion, A1R stimulation of the heart is associated with PLC-initiated PKC-ε translocation and association with RACK2.

CLINICAL TRIAL OF HUMAN GONADOTROPHINS

1966 ◽  
Vol 53 (3_Suppl) ◽  
pp. S3-S26 ◽  
Author(s):  
A. C. Crooke ◽  
W. R. Butt ◽  
P. V. Bertrand
Keyword(s):  
Clinical Trial ◽  
Dose Response ◽  
Positive Response ◽  
Test Dose ◽  
Sufficient Data ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Individual Sensitivity ◽  
The Difference ◽  
The Times

ABSTRACT Thirteen patients with prolonged secondary amenorrhoea and 5 with anovular cycles each provided sufficient data to establish their individual sensitivity to FSH. The parameters used were based on the rise in excretion of oestriol and of pregnanediol. The sensitivity expressed as the ED 50 (that dose which is effective in 50 per cent of times it is given) varied between patients over at least a sevenfold range but the difference between the 2 groups of patients was not significant. After adjusting for differences between patients a dose-response relationship was established and it was found that a dose equal to half the ED 50 would be expected to produce a response in less than Io per cent of the times it is given while a dose equal to twice the ED 50 would be expected to produce a response in more than go per cent of the times it is given. Such a dose would be likely to produce an excessive response. An excessive response occurred three times in 140 months of treatment. Sixteen of the I8 patients became pregnant. The 2 who failed gave up treatment prematurely. A test of individual patient's sensitivity to FSH was established which depended on single injections of the hormone mixed with HCG. The test was repeated at 2 to 3 weekly intervals with increasing dosages until a positive response was obtained as judged by an increase in excretion of oestriol. The rate at which the dose should be increased was investigated and a 30 per cent rate was selected. When the effective test dose was established a standard schedule of dosages was recommended for treatment using 3 equal doses of FSH in 8 days and HCG on the tenth.

scholarly journals EFFECT OF THERAPEUTIC ULTRASOUND IN THE RELEASE AND PERMEATION OF CAFFEINE LIPOSOMES IN VERTICAL DIFFUSION SYSTEMS

2019 ◽  
Vol 16 (31) ◽  
pp. 274-280
Author(s):  
Luana MARQUES ◽  
João Alberto TASSINARY ◽  
Bárbara SCHMIDTT ◽  
Paula BIANCHETTI ◽  
Simone STÜLP
Keyword(s):  
Stratum Corneum ◽  
Skin Resistance ◽  
Therapeutic Ultrasound ◽  
Skin Permeability ◽  
Vertical Diffusion ◽  
Topical Formulations ◽  
Diffusion Systems ◽  
Release Analysis ◽  
The Difference ◽  
The Times

The development of new topical formulations provides new release systems of substances that are capable of outline the limitations imposed by the skin permeability of the stratum corneum. A resource used to reduce skin resistance is Therapeutic Ultrasound that by phonophoresis provides adequate concentration of the active to the skin. The study compares the effect of the release and permeation caffeine liposomes 5% combined with ultrasound. In release analysis, caffeine liposomes in times of 5, 10, 15 and 20 minutes were used with the ultrasound. In the permeation analysis, biomembrane snake skin was used in a time of 20 minutes. A difference in the release of the substance was observed, but when compared with the times using the ultrasound, the difference was noticed more markedly so. In terms of permeation, there was a greater increase associated with ultrasound. Thus, the results suggest the importance of phonophoresis increase in permeation of substances on the skin.

Subcellular distribution of sodium pump isoform subunits in mammalian cardiac myocytes

1996 ◽  
Vol 270 (4) ◽  
pp. C1221-C1227 ◽  
Author(s):  
A. A. McDonough ◽  
Y. Zhang ◽  
V. Shin ◽  
J. S. Frank
Keyword(s):  
Guinea Pig ◽  
Driving Force ◽  
Human Heart ◽  
Sodium Pump ◽  
Immunogold Labeling ◽  
Guinea Pig Heart ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Na Pump ◽  
T Tubules

The cardiac Na+ pump (Na+ -K+ -ATPase) provides the driving force for the Na+/Ca2+ exchanger, a determinant of intracellular Ca2+ stores. Three Na+ pump alpha-catalytic subunit isoforms are expressed in human heart, alpha1 and alpha2 are expressed in rat heart, and only alpha1 is expressed in guinea pig heart. The objective of this study was to determine whether there are isoform-specific patterns of expression in the transverse tubules (T tubules) vs. the peripheral sarcolemma. In adult rat cardiomyocytes, anti-alpha1-specific antibodies labeled the T tubules more intensely than the peripheral sarcolemma, in which labeling was patchy, the same pattern reported for distribution of the Na+/Ca2+ exchanger (J. S. Frank, G. Mottino, D. Reid, R. S. Molday, and K. D. Philipson, J. Cell Biol. 117: 337-345, 1992), whereas anti-alpha2- and anti-beta1-antibodies uniformly labeled T tubules and peripheral sarcolemma. In guinea pig cardiomyocytes, an anti-alpha-antibody against an extracellular epitope evenly labeled the peripheral sarcolemma and T tubules, and immunogold labeling demonstrated coincidence of alpha-subunits and intramembranous particles in sarcolemma. In summary, Na+ pumps are located in both peripheral sarcolemma and T tubules of cardiomyocytes expressing either multiple or single Na+ pump isoforms.

scholarly journals V. Magnetic declination at Kew Observatory, 1890 to 1900

1908 ◽  
Vol 208 (427-440) ◽  
pp. 205-246 ◽  
Keyword(s):  
Infinite Number ◽  
General Trend ◽  
Practical Interest ◽  
Arithmetic Mean ◽  
Time Interval ◽  
Continuous Line ◽  
Appropriate Treatment ◽  
The Difference ◽  
The Times ◽  
Quiet Day

In 1903 I carried out an analysis—referred to here for brevity as A—of the results given by the Kew magnetographs on “quiet” days during the 11 years 1890 to 1900. This investigation brought to light various novel phenomena. It was subsequently shown—in a paper to be referred to as B—that these phenomena are equally true of “quiet” days at Falmouth. Some of the phenomena suggested the possibility of differences of a certain kind between quiet days and other undisturbed days, and between ordinary days and disturbed days. To prosecute this enquiry, it was necessary to make an analysis of the data from all days at Kew from 1890 to 1900. Declination being the element of most practical interest, and least open to instrumental uncertainties, it was decided to treat it thoroughly in the first instance. In measuring the quiet day curves at Kew—a practice instituted in 1890—it has been usual to smooth them when any little irregularities occur, by drawing a free­- hand pencil trace following the general trend. It was decided, with some hesitation, to continue the practice, so that the results from all days should be as strictly comparable as possible with those from quiet days. The nature of the difficulties will be understood from the accompanying diagram. The continuous line curve ABCDEFQRS represents a hypothetical photographic record. The dotted line AB'C'R' represents the smoothed curve. When the object aimed at is the regular diurnal inequality, it will probably be generally conceded that the method of smoothing adopted is satisfactory so far as the wave-like portion ABCDE is concerned, at least so long as the interval of time corresponding to this portion is under an hour. If, how­ever, the times from A to B and from B to C were each an hour, the procedure would be disapproved by some authorities, who would argue that the free-hand curve should always be drawn so that its ordinate at any particular hour should represent the arithmetic mean of an infinite number of ordinates, uniformly distributed in time throughout the preceding and succeeding 30 minutes. It should, however, be remembered that the exact instant when an hour falls is really arbitrary. One observer may use Greenwich time, another local, and if the smoothing were carried out in accordance with the view last mentioned, it might make all the difference which choice happened to have been made. A disturbance such as QBS presents difficulties of another kind. If the time interval from Q to S is only a few minutes, and the general trend of the curve is very clearly shown, and closely similar to that of the average day, there can, I think, be little doubt that the best plan—at least when diurnal inequalities are concerned—is simply to disregard the disturbance altogether. If, however, the time from Q to S is considerable, and the general trend of the curve not clearly shown, the appropriate treatment is difficult to determine.

scholarly journals Dare to care

2019 ◽  
Vol 20 (1) ◽  
pp. 25-43
Author(s):  
Anita Calvert
Keyword(s):  
Everyday Life ◽  
Care Home ◽  
The Self ◽  
Moral Principles ◽  
Kent County ◽  
Life Threatening ◽  
The Difference ◽  
New Perspective ◽  
The Times ◽  
Threatening Situation

Paper is divided into two parts. The first contains two philosophical discussions about comprehension of courage and the second focuses on the findings in an empirical study with care home managers about the virtue of courage. First discussion revolves around the question whether the virtue of courage is expressed a) only in life–threatening situations or is it a virtue trained and exemplified in b) everyday life settings, while the second emphasises the difference between i) courage of efficiency as a skill and ii) courage of excellence as a virtue. Arguments here support a vision of courage as the virtue of excellence expressed in everyday life settings. The second part of the paper highlights a new perspective of courage with regards to the notion of care towards the aim of the courageous endeavour. The ‘courage of care’ supports the idea that the courage practised as the virtue of excellence aims to develop the moral character of the actor fundamentally outside of the life–threatening situation. Care for the self, other people, animals and intangible moral principles inspire us to do brave deeds. Thus, by accepting Alasdair MacIntyre’s statements that a) in the times of the peace managers represent moral idols and b) idea that the notion of courage should be closely related to the practice of care and compassion, the research continued with the interviews with the care home managers in Kent county in England. Conversations with care home managers released further insights into how care and compassion influence the understanding of the virtue of courage.

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