Measurement of myofilament calcium sensitivity at physiological temperature in intact cardiac trabeculae

2006 ◽  
Vol 290 (5) ◽  
pp. H2092-H2097 ◽  
Author(s):  
Kenneth D. Varian ◽  
Sripriya Raman ◽  
Paul M. L. Janssen
Keyword(s):  
Steady State ◽  
Calcium Sensitivity ◽  
Cardiac Contraction ◽  
Adrenergic Stimulation ◽  
Rightward Shift ◽  
Physiological Temperature ◽  
Sensitivity Assessment ◽  
Before And After ◽  
State Force ◽  
Myofilament Calcium Sensitivity

Cardiac contraction-relaxation coupling is determined by both the free intracellular calcium concentration ([Ca2+]i) and myofilament properties. We set out to develop a technique where we could assess these parameters (twitch and steady-state force [Ca2+]i) under near physiological conditions. Bis-fura-2 was iontophorically introduced into ultrathin rat trabeculae preparations to monitor the [Ca2+]i, and steady-state contractures were achieved by using a modified Krebs-Henseleit solution containing high K+. During K+ contractures, the very slow changes in [Ca2+]i and force development were in equilibrium and allowed for the construction of a steady-state, force-[Ca2+]i relationship. Twitch contractions before and after this myofilament calcium sensitivity assessment were unaltered, and this protocol could be repeated several times. For the first time, this novel protocol allows us to measure myofilament calcium sensitivity under physiological temperature. Not only do the data so obtained allow us to assess myofilament calcium sensitivity, the data also will allow us, in the same preparation under nearly identical conditions, to compare the dynamic to the steady-state, force-calcium relationship. To test whether the steady-state relationship between force and calcium in our novel protocol reproduces expected changes, we determined this relationship in the presence of isoproterenol and under acidosis and alkalosis. As expected, β-adrenergic stimulation resulted in an increase of calcium amplitude and twitch force and a desensitization of the myofilaments as indicated by a rightward shift of the obtained steady-state, force-calcium relationship. An increase in pH shifted the curve leftward, whereas a decrease in pH resulted in the expected rightward shift.

scholarly journals Myofilament Calcium Sensitivity: Role in Regulation of In vivo Cardiac Contraction and Relaxation

2016 ◽  
Vol 7 ◽  
Author(s):  
Jae-Hoon Chung ◽  
Brandon J. Biesiadecki ◽  
Mark T. Ziolo ◽  
Jonathan P. Davis ◽  
Paul M. L. Janssen
Keyword(s):  
Calcium Sensitivity ◽  
Cardiac Contraction ◽  
Contraction And Relaxation ◽  
Myofilament Calcium Sensitivity

scholarly journals Acute exposure to progesterone attenuates cardiac contraction by modifying myofilament calcium sensitivity in the female mouse heart

2017 ◽  
Vol 312 (1) ◽  
pp. H46-H59 ◽  
Author(s):  
Hirad A. Feridooni ◽  
Jennifer K. MacDonald ◽  
Anjali Ghimire ◽  
W. Glen Pyle ◽  
Susan E. Howlett
Keyword(s):  
Ventricular Myocytes ◽  
Heart Function ◽  
Calcium Sensitivity ◽  
Cardiac Contraction ◽  
Mouse Heart ◽  
Sodium Pentobarbital ◽  
Serum Progesterone ◽  
Time Courses ◽  
Myofilament Calcium Sensitivity ◽  
In Pregnancy

Acute application of progesterone attenuates cardiac contraction, although the underlying mechanisms are unclear. We investigated whether progesterone modified contraction in isolated ventricular myocytes and identified the Ca2+ handling mechanisms involved in female C57BL/6 mice (6–9 mo; sodium pentobarbital anesthesia). Cells were field-stimulated (4 Hz; 37°C) and exposed to progesterone (0.001–10.0 μM) or vehicle (35 min). Ca2+ transients (fura-2) and cell shortening were recorded simultaneously. Maximal concentrations of progesterone inhibited peak contraction by 71.4% (IC50 = 160 ± 50 nM; n = 12) and slowed relaxation by 75.4%. By contrast, progesterone had no effect on amplitudes or time courses of underlying Ca2+ transients. Progesterone (1 µM) also abbreviated action potential duration. When the duration of depolarization was controlled by voltage-clamp, progesterone attenuated contraction and slowed relaxation but did not affect Ca2+ currents, Ca2+ transients, sarcoplasmic reticulum (SR) content, or fractional release of SR Ca2+. Actomyosin MgATPase activity was assayed in myofilaments from hearts perfused with progesterone (1 μM) or vehicle (35 min). While maximal responses to Ca2+ were not affected by progesterone, myofilament Ca2+ sensitivity was reduced (EC50 = 0.94 ± 0.01 µM for control, n = 7 vs. 1.13 ± 0.05 μM for progesterone, n = 6; P < 0.05) and progesterone increased phosphorylation of myosin binding protein C. The effects on contraction were inhibited by lonaprisan (progesterone receptor antagonist) and levosimendan (Ca2+ sensitizer). Unlike results in females, progesterone had no effect on contraction or myofilament Ca2+ sensitivity in age-matched male mice. These data indicate that progesterone reduces myofilament Ca2+ sensitivity in female hearts, which may exacerbate manifestations of cardiovascular disease late in pregnancy when progesterone levels are high. NEW & NOTEWORTHY We investigated myocardial effects of acute application of progesterone. In females, but not males, progesterone attenuates and slows cardiomyocyte contraction with no effect on calcium transients. Progesterone also reduces myofilament calcium sensitivity in female hearts. This may adversely affect heart function, especially when serum progesterone levels are high in pregnancy. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/acute-progesterone-modifies-cardiac-contraction/ .

Modulation of carotid baroreflex responsiveness in man: effects of posture and propranolol

1976 ◽  
Vol 41 (3) ◽  
pp. 383-387 ◽  
Author(s):  
D. L. Eckberg ◽  
F. M. Abboud ◽  
A. L. Mark
Keyword(s):  
Angina Pectoris ◽  
Supine Position ◽  
Baroreflex Sensitivity ◽  
Pulse Interval ◽  
Upright Posture ◽  
Adrenergic Stimulation ◽  
Interval Prolongation ◽  
Carotid Baroreflex ◽  
Before And After ◽  
Autonomic Blockade

Carotid baroreceptors were stimulated with graded neck suction in supine and standing volunteers, before and after autonomic blockade, to determine the influence of posture on baroreflex responsiveness. Propranolol significantly augmented baroreflex pulse interval prolongation in the supine position. Upright posture did not modify baroreflex pulse interval responses prior to propranolol, but significantly augmented responses after propranolol. The results suggest that standing enhances baroreflex sensitivity, but that under normal circumstances, this effect is masked by beta-adrenergic stimulation. Augmentation of baroreflex pulse interval prolongation in the supine and standing positions by propranolol may contribute to the effectiveness of this drug in angina pectoris and labile hypertension.

scholarly journals Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle

2014 ◽  
Vol 307 (10) ◽  
pp. H1487-H1496 ◽  
Author(s):  
Sander Land ◽  
Steven A. Niederer ◽  
William E. Louch ◽  
Åsmund T. Røe ◽  
Jan Magnus Aronsen ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Takotsubo Cardiomyopathy ◽  
Troponin I ◽  
Contractile Function ◽  
Single Cells ◽  
Apical Ballooning ◽  
Calcium Sensitivity ◽  
Takotsubo Syndrome ◽  
Adrenergic Stimulation ◽  
Inotropic Effects

In Takotsubo cardiomyopathy, the left ventricle shows apical ballooning combined with basal hypercontractility. Both clinical observations in humans and recent experimental work on isolated rat ventricular myocytes suggest the dominant mechanisms of this syndrome are related to acute catecholamine overload. However, relating observed differences in single cells to the capacity of such alterations to result in the extreme changes in ventricular shape seen in Takotsubo syndrome is difficult. By using a computational model of the rat left ventricle, we investigate which mechanisms can give rise to the typical shape of the ventricle observed in this syndrome. Three potential dominant mechanisms related to effects of β-adrenergic stimulation were considered: apical-basal variation of calcium transients due to differences in L-type and sarco(endo)plasmic reticulum Ca2+-ATPase activation, apical-basal variation of calcium sensitivity due to differences in troponin I phosphorylation, and apical-basal variation in maximal active tension due to, e.g., the negative inotropic effects of p38 MAPK. Furthermore, we investigated the interaction of these spatial variations in the presence of a failing Frank-Starling mechanism. We conclude that a large portion of the apex needs to be affected by severe changes in calcium regulation or contractile function to result in apical ballooning, and smooth linear variation from apex to base is unlikely to result in the typical ventricular shape observed in this syndrome. A failing Frank-Starling mechanism significantly increases apical ballooning at end systole and may be an important additional factor underpinning Takotsubo syndrome.

PKC catalytic subunit and phenylephrine induce a comparable decrease in myofilament calcium sensitivity

2007 ◽  
Vol 42 (6) ◽  
pp. S46
Author(s):  
Judit Barta ◽  
Jolanda van der Velden ◽  
Nicky M. Boontje ◽  
Ruud Zaremba ◽  
Ger J.M. Stienen
Keyword(s):  
Calcium Sensitivity ◽  
Catalytic Subunit ◽  
Myofilament Calcium Sensitivity

Increased alpha 1-adrenergic vascular sensitivity during development of hypertension in conscious dogs

1993 ◽  
Vol 264 (4) ◽  
pp. H1259-H1268 ◽  
Author(s):  
N. Uemura ◽  
D. E. Vatner ◽  
Y. T. Shen ◽  
J. Wang ◽  
S. F. Vatner
Keyword(s):  
Adrenergic Receptor ◽  
Peripheral Resistance ◽  
Aortic Pressure ◽  
Conscious Dogs ◽  
Aortic Tissue ◽  
Ang Ii ◽  
Receptor Density ◽  
Adrenergic Stimulation ◽  
Before And After ◽  
Vascular Responsiveness

The goal of this study was to determine whether enhanced vascular responsiveness during the development of perinephritic hypertension is selective or nonspecific. The effects of graded infusions of norepinephrine (NE), phenylephrine (PE), angiotensin II (ANG II), and vasopressin (VP) were examined on mean arterial pressure, total peripheral resistance (TPR), and aortic pressure-diameter relationships in conscious dogs. NE increased TPR significantly greater (P < 0.01) in hypertension than normotension, as did PE infusion, whereas ANG II and VP increased TPR similarly before and after hypertension. Analysis of aortic pressure-diameter relationships also demonstrated significant (P < 0.05) shifts in response to NE and PE, but not ANG II and VP, during the development of hypertension. In normotensive dogs, low doses of ANG II infusion also enhanced the vasoconstrictor response not only to NE and PE but also to VP. In contrast to what was observed in hypertension, in the presence of ANG II infusion after ganglionic blockade, enhanced responses to PE and NE were no longer observed. The alpha 1-adrenergic receptor density in membrane preparations from aortic tissue, as determined by [3H]prazosin binding, was higher (P < 0.05) in hypertensive dogs than control dogs. Thus the vascular responsiveness in the aorta and resistance vessels is enhanced to alpha 1-adrenergic stimulation, but not to all vasoconstrictors, during developing perinephritic hypertension. The mechanism appears to involve increased alpha 1-adrenergic receptor density.

The effects of Acute and Chronic β-Adrenoceptor Blockade on the Myofibrillar Contractile System in the Dog Heart

1984 ◽  
Vol 67 (2) ◽  
pp. 259-267 ◽  
Author(s):  
M. K. Davies ◽  
P. Cummins ◽  
W. A. Littler
Keyword(s):  
Calcium Sensitivity ◽  
Maximal Activity ◽  
Biopsy Specimens ◽  
Contractile System ◽  
Chronic Therapy ◽  
Before And After ◽  
Adaptive Effect ◽  
Electrophoretic Techniques ◽  
Myocardial Contractile ◽  
And Function

1. Electrophoretic and enzyme techniques have been used to study the structure and function of the contractile protein system in the myocardium of dogs before and after β-adrenoceptor blockade. Animals were examined after acute β-adrenoceptor blockade by using intravenous atenolol (0.2 mg/kg) and following chronic therapy with oral atenolol (100 mg twice daily) for a mean period of 106 days. 2. Two-dimensional polyacrylamide-gel electrophoretic techniques were used to examine the myocardial contractile and regulatory proteins present in endomyocardial biopsy specimens obtained after acute and chronic β-adrenoceptor blockade. No differences in charge, molecular weight or the relative proportions of actin, myosin light chains, tropomyosin or troponin-C were seen after either acute or chronic β-adrenoceptor blockade. 3. The maximal activity and calcium sensitivity of the myofibrillar adenosine triphosphatase (ATPase) was also unchanged after acute and chronic atenolol therapy. 4. It is concluded that β-adrenoceptor blockade has no significant adaptive effect on the structural or functional properties of the myofibril.

The Study of Dynamic Response to Acute Hemorrhage by Pulse Spectrum Analysis

2006 ◽  
Vol 34 (03) ◽  
pp. 449-460 ◽  
Author(s):  
Yu Hsin Chang ◽  
Chia I Tsai ◽  
Jaung Geng Lin ◽  
Yue Der Lin ◽  
Tsai Chung Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Spectrum Analysis ◽  
Pulse Spectrum ◽  
Acute Hemorrhage ◽  
Arterial Blood ◽  
Percentage Difference ◽  
Before And After

Traditional Chinese Medicine (TCM) holds that Blood and Qi are fundamental substances in the human body for sustaining normal vital activity. The theory of Qi, Blood and Zang-Fu contribute the most important theoretical basis of human physiology in TCM. An animal model using conscious rats was employed in this study to further comprehend how organisms survive during acute hemorrhage by maintaining the functionalities of Qi and Blood through dynamically regulating visceral physiological conditions. Pulse waves of arterial blood pressure before and after the hemorrhage were taken in parallel to pulse spectrum analysis. Percentage differences of mean arterial blood pressure and harmonics were recorded in subsequent 5-minute intervals following the hemorrhage. Data were analyzed using a one-way analysis of variance (ANOVA) with Duncan's test for pairwise comparisons. Results showed that, within 30 minutes following the onset of acute hemorrhage,the reduction of mean arterial blood pressure was improved from 62% to 20%. Throughout the process, changes to the pulse spectrum appeared to result in a new balance over time. The percentage differences of the second and third harmonics, which were related to kidney and spleen, both increased significantly than baseline and towards another steady state. Apart from the steady state resulting from the previous stage, the percentage difference of the 4th harmonic decreased significantly to another steady state. The observed change could be attributed to the induction of functional Qi, and is a result of Qi-Blood balancing activity that organisms hold to survive against acute bleeding.

Encoding of amplitude and rate of forces applied to the teeth by human periodontal mechanoreceptive afferents

1994 ◽  
Vol 72 (4) ◽  
pp. 1734-1744 ◽  
Author(s):  
M. Trulsson ◽  
R. S. Johansson
Keyword(s):  
Steady State ◽  
Discharge Rate ◽  
Inferior Alveolar Nerve ◽  
Steady State Response ◽  
Force Amplitude ◽  
Stimulus Response ◽  
State Response ◽  
Dynamic Sensitivity ◽  
Linear Relationships ◽  
State Force

1. The encoding of force amplitude and force rate by human periodontal mechanoreceptive afferents was studied. Recordings were obtained from 19 single periodontal afferents in the inferior alveolar nerve with the use of tungsten microelectrodes. Loads consisting of a force increase (loading ramp), a phase of maintained force (static phase), and a force decrease (unloading ramp) were applied to the receptor bearing tooth, which was most often an incisor. The static forces applied ranged between 0.05 and 5 N, and the rate of force applied during the loading ramps ranged between 0.4 and 70 N/s. The forces were primarily applied in one of six directions (lingual, labial, mesial, distal, upward, or downward) that evoked the greatest discharge activity. 2. For each force application, the steady-state response was defined as the mean discharge rate during a 1-s period starting 0.5 s after the end of the loading ramp. Most afferents (15/19) exhibited a “hyperbolic” (viz., negatively accelerating) relationship between the amplitude of the stimulation force and the steady-state response, featuring a pronounced saturation tendency: the highest sensitivity to changes in static force was observed at force levels below 1 N. At higher force levels the sensitivity gradually diminished. Moreover, the dynamic sensitivity similarly decreased with increasing amplitude of static background force. For a subsample of afferents studied, comparable stimulus-response relationships were obtained in directions other than the most responsive one, but the discharge rates were lower. 3. In contrast to the response of most afferents, four (4/19) differed in that they consistently exhibited a nearly linear relationship between force amplitude and the steady-state response. Moreover, these afferents maintained their dynamic sensitivity as the amplitude of the background force was increased. 4. The steady-state response of all afferents was well described as a constant times F/ (F + c), where F represents the steady-state force, and c the force generating one-half the estimated maximum discharge rate that could be evoked by steady-state force stimulation. The c-parameter was on average 0.42 N (range 0.05–1.1 N) for the afferents exhibiting hyperbolic stimulus-response relationships. In contrast it ranged between 5 and 22 N for those exhibiting “nearly linear” relationships. A hypothetical model of the mechanics of the periodontal ligament supporting the F/(F + c) transform is proposed. 5. A general transfer function was developed to predict the instantaneous discharge rate of an individual afferent to arbitrary force profiles applied to the receptor bearing tooth.(ABSTRACT TRUNCATED AT 400 WORDS)

Modelling Age Differences in Isometric Elbow Flexion Using Hill's Three-Element Visco-Elastic Model

1993 ◽  
Vol 37 (2) ◽  
pp. 202-205
Author(s):  
R. Darin Ellis ◽  
Kentaro Kotani
Keyword(s):  
Mechanical Properties ◽  
Steady State ◽  
Age Differences ◽  
Elbow Flexion ◽  
Model Parameters ◽  
Elastic Model ◽  
Tissue Elasticity ◽  
Age Related ◽  
Complex Models ◽  
State Force

A visco-elastic model of the mechanical properties of muscle was used to describe age-differences in the buildup of force in isometric elbow flexion. Given information from the literature on age-related physiological changes, such as decreasing connective-tissue elasticity, one would expect changes in the mechanical properties of skeletal muscle and their related model parameters. Force vs. time curves were obtained for 7 young (aged 21–27) and 7 old (aged 69–83) female subject. There were significant age group differences in steady-state force level and the best fitting model parameters. In particular, the viscous damping element of the model plays a large role in describing the increased time to reach steady-state force levels in the older subject group. Implications of this research include incorporating parameter differences into more complex models, such as crash impact models.

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