Altered pyruvate dehydrogenase control and mitochondrial free Ca2+ in hearts of cardiomyopathic hamsters

1993 ◽  
Vol 264 (6) ◽  
pp. H2188-H2197 ◽  
Author(s):  
F. Di Lisa ◽  
C. Z. Fan ◽  
G. Gambassi ◽  
B. A. Hogue ◽  
I. Kudryashova ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Pyruvate Dehydrogenase ◽  
Adrenergic Stimulation ◽  
Isolated Hearts ◽  
Maximal Activation ◽  
Cardiomyopathic Hamsters ◽  
Healthy Control ◽  
Oxoglutarate Dehydrogenase ◽  
And Performance ◽  
Tricarboxylate Cycle

The fraction of total pyruvate dehydrogenase in the active, dephosphorylated form is much lower in the glucose-perfused isolated hearts of two myopathic strains of Syrian hamster (BIO 14.6 and TO-2) than in the hearts of healthy control animals (F1B). The myopathic hearts also develop significantly less pressure under these conditions. Experiments with isolated myocytes from the BIO 14.6 heart reveal that intramitochondrial free Ca2+ ([Ca2+]m), a positive effector of pyruvate dehydrogenase interconversion, rises much less in response to a protocol of increased frequency of electrical stimulation and adrenergic stimulation than does [Ca2+]m in cells from the healthy control animals (viz from 248 +/- 15 to 348 +/- 44 nM in BIO 14.6 vs. from 241 +/- 35 to 830 +/- 124 nM in F1B, at 4 Hz). As the concentration of Ca2+ that produces half-maximal activation of pyruvate dehydrogenase within mitochondria is 650 nM, this difference between strains is likely the mechanism of the altered enzyme interconversion. The lesser response of [Ca2+]m to electrical stimulation in the BIO 14.6 cells probably results mainly from smaller systolic transients in cytosolic free Ca2+ in response to excitation of single myocytes from the BIO 14.6 animal. Lowered values of [Ca2+]m within the range described would compromise not only pyruvate dehydrogenase activity, but also flux through the tricarboxylate cycle in the myopathic heart, owing to the sensitivity of 2-oxoglutarate dehydrogenase to Ca2+. This may explain the decreased activity of oxidative phosphorylation and performance of work in the myopathic heart.

scholarly journals Role of Ca2+ ions in the regulation of intramitochondrial metabolism in rat heart. Evidence from studies with isolated mitochondria that adrenaline activates the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes by increasing the intramitochondrial concentration of Ca2+

1984 ◽  
Vol 218 (1) ◽  
pp. 235-247 ◽  
Author(s):  
J G McCormack ◽  
R M Denton
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Rat Heart ◽  
Rabbit Heart ◽  
Similar Degree ◽  
Isolated Mitochondria ◽  
A Value ◽  
Rat Hearts ◽  
Maximal Activation ◽  
Oxoglutarate Dehydrogenase

Increases in the amount of active, non-phosphorylated, pyruvate dehydrogenase which result from the perfusion of rat hearts with adrenaline were still evident during the preparation of mitochondria in sucrose-based media containing EGTA (at 0 degrees C) and their subsequent incubation at 30 degrees C in Na+-free KCl-based media containing respiratory substrates and EGTA. The differences from control values gradually diminished with time of incubation, but were still present after 8 min. Similar increases resulting from an increase in the concentration of Ca2+ in the perfusing medium also persisted. However, similar increases caused by 5 mM-pyruvate were only maintained during the preparation of mitochondria, not their incubation. Parallel increases, within incubated mitochondria, were found in the activity of the 2-oxoglutarate dehydrogenase complex assayed at a non-saturating concentration of 2-oxoglutarate. The enhancement of the activities of both of these Ca2+-sensitive enzymes within incubated mitochondria as a result of perfusion with adrenaline or a raised concentration of Ca2+ in the medium could be abolished within 1 min by the presence of 10 mM-NaCl. This effect of Na+ was blocked by 300 microM-diltiazem, which has been shown to inhibit Na+-induced egress of Ca2+ from rabbit heart mitochondria [Vághy, Johnson, Matlib, Wang & Schwartz (1982) J. Biol. Chem. 257, 6000-6002]. The enhancements could also be abolished by increasing the extramitochondrial concentration of Ca2+ to a value where it caused maximal activation of the enzymes within control mitochondria. The results are consistent with the hypothesis that adrenaline activates rat heart pyruvate dehydrogenase by increasing the intramitochondrial concentration of Ca2+ and that this increase persists through to incubated mitochondria. Support for this conclusion was obtained by the yielding of a similar set of results from parallel experiments performed on control mitochondria that had firstly been preincubated (under conditions of steady-state Ca2+ cycling across the inner membrane) with sufficient proportions of Ca-EGTA buffers to achieve a similar degree of Ca2+-activation of pyruvate dehydrogenase (as caused by adrenaline) and had then undergone the isolation procedure again.

scholarly journals Physical activity in elderly

2015 ◽  
Vol 25 (4) ◽  
pp. 249 ◽  
Author(s):  
Jan Cvecka ◽  
Veronika Tirpakova ◽  
Milan Sedliak ◽  
Helmut Kern ◽  
Winfried Mayr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Electrical Stimulation ◽  
Muscle Mass ◽  
Irreversible Process ◽  
Significant Decline ◽  
Positive Effects ◽  
Age Related ◽  
And Performance ◽  
And Function ◽  
Age Related Changes

Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared.

Adrenergic Stimulation of the Rat Diencephalon and its Effect on Food Intake and Hoarding Activity

1970 ◽  
Vol 22 (2) ◽  
pp. 125-132 ◽  
Author(s):  
J. E. Blundell ◽  
L. J. Herberg
Keyword(s):  
Electrical Stimulation ◽  
Food Intake ◽  
Food Deprivation ◽  
Lateral Hypothalamus ◽  
Adrenergic Stimulation ◽  
Feeding Mechanism ◽  
Stimulation Of ◽  
Nutritional Depletion

The diencephalic area most sensitive to microinjections of noradrenaline lay outside the area of the lateral hypothalamus in which feeding can be produced by electrical stimulation. Injection of either area, including injections that caused increased feeding, failed to have any effect on hoarding activity. Since hoarding can be elicited both by food deprivation and by electrical stimulation of the lateral hypothalamus, these findings indicate biochemical, anatomical and motivational differences between the central feeding mechanism sensitive to adrenergic stimulation, and that responding to electrical stimulation or nutritional depletion. The former mechanism may be disinhibitory; the latter, excitatory.

Cardiac nicotinic receptors show β-subunit dependent compensatory changes

2021 ◽  
Author(s):  
Katarina Targosova ◽  
Matej Kucera ◽  
Zuzana Kilianova ◽  
Lubica Slobodova ◽  
Kristina Szmicsekova ◽  
...  
Keyword(s):  
Heart Rate ◽  
Muscarinic Receptors ◽  
Nicotinic Receptors ◽  
Isolated Heart ◽  
High Dose ◽  
Β Subunit ◽  
Adrenergic Stimulation ◽  
Relative Expression ◽  
Isolated Hearts ◽  
Heart Functions

Nicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4 and α3 subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking β4 NR subunit, increased levels of β2 subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in β4-/- hearts were associated with increased basal heart rate and impaired response to a high dose of acetylcholine upon adrenergic stimulation. In support of the proposed plasticity of cardiac NRs, our results confirmed subunit-dependent compensatory changes to missing cardiac NRs subunits with consequences on isolated heart physiology.

Alterations in cardiac SR Ca2+-release channels during development of heart failure in cardiomyopathic hamsters

1998 ◽  
Vol 274 (1) ◽  
pp. H1-H7 ◽  
Author(s):  
Takeshi Ueyama ◽  
Tomoko Ohkusa ◽  
Yuji Hisamatsu ◽  
Yasuma Nakamura ◽  
Takeshi Yamamoto ◽  
...  
Keyword(s):  
Heart Failure ◽  
Early Stage ◽  
Ryanodine Receptors ◽  
Left Ventricular ◽  
Binding Assays ◽  
Immunoblot Assay ◽  
Significant Difference ◽  
Cardiac Pump Function ◽  
Cardiomyopathic Hamsters ◽  
Healthy Control

The cardiomyopathic Syrian hamster develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, cardiac dilatation, and congestive heart failure. This study aimed to identify alterations in cardiac mechanical function and in the cellular content of sarcoplasmic reticulum (SR) Ca2+-release channels (ryanodine receptors, RyR) in the heart of the UM-X7.1 cardiomyopathic hamster during the development of heart failure. Experimental and healthy control hamsters were examined at 8, 18, and 28 wk of age. The UM-X7.1 hamsters had developed left ventricular (LV) hypertrophy at 8 wk and a marked LV dilatation at 18–28 wk. During the latter stage, the UM-X7.1 hamster hearts showed global hypokinesis. Equilibrium binding assays of high-affinity sites for [3H]ryanodine were performed in ventricular homogenate preparations. There was no significant difference between the two groups in the maximum number of [3H]ryanodine binding sites (Bmax) at either 8 or 18 wk of age, although the cardiac pump function was impaired in UM-X7.1 hamsters at 18 wk of age. By 28 wk, Bmax was significantly lower in the UM-X7.1 hamsters. Quantitative immunoblot assay revealed that the content of RyR protein in cardiomyopathic hearts, which was increased at the early stage, declined to below normal as heart failure advanced. These results suggest that the number of RyR in the UM-X7.1 cardiomyopathic hamsters was preserved at both the hypertrophic and early stages of heart failure with a possibly compensatory increase in the level of protein expression, although the cardiac function already showed a tendency to be impaired.

Enhancement by vasopressin of adrenergic responses in human mesenteric arteries

1997 ◽  
Vol 272 (3) ◽  
pp. H1087-H1093 ◽  
Author(s):  
P. Medina ◽  
I. Noguera ◽  
M. Aldasoro ◽  
J. M. Vila ◽  
B. Flor ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Animal Experiments ◽  
Mesenteric Arteries ◽  
Organ Bath ◽  
Adrenergic Stimulation ◽  
Response Curves ◽  
Receptor Stimulation ◽  
Half Maximal Effective Concentration

Vasopressin not only acts directly on blood vessels through V1-receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vitro and in vivo. The aim of the present study was to investigate whether subpressor concentrations of vasopressin could modify the constrictor responses to norepinephrine and electrical stimulation of the perivascular nerves in human mesenteric arteries. Human mesenteric artery rings (3-3.5 mm long, 0.8-1.2 mm OD) were obtained from 38 patients undergoing abdominal operations. The arterial rings were suspended in organ bath chambers for isometric recording of tension. Vasopressin (3 x 10(-11) M) enhanced the contractions elicited by electrical stimulation at 2, 4, and 8 Hz (by 100, 100, and 72%, respectively) and produced a leftward shift of the concentration-response curves to norepinephrine (half-maximal effective concentration decreased from 2.2 x 10(-6) to 5.0 x 10(-7) M; P < 0.05) without any alteration in maximal contractions. Vasopressin also potentiated KCl- and calcium-induced contractions. The V1-receptor antagonist 1-[beta-mercapto-beta,beta-cyclopentamethylenepropionic acid-2-O-methyl-tyrosine, 8-arginine]vasopressin (10(-6) M) prevented the potentiation evoked by vasopressin in all cases. The calcium antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical stimulation and norepinephrine induced by vasopressin but abolished KCl-induced contractions. The results suggest that vasopressin, in addition to its direct vasoconstrictor effect, strongly potentiates the responses to adrenergic stimulation and KCl depolarization. Both the direct and indirect effects of vasopressin appear to be mediated by V1-receptor stimulation. The amplifying effect of vasopressin on constrictor responses may be relevant in those clinical situations characterized by increased plasma vasopressin levels.

scholarly journals Switched Control of Motor Assistance and Functional Electrical Stimulation for Biceps Curls

2020 ◽  
Vol 10 (22) ◽  
pp. 8090
Author(s):  
Courtney Rouse ◽  
Brendon Allen ◽  
Warren Dixon
Keyword(s):  
Electrical Stimulation ◽  
Functional Electrical Stimulation ◽  
Biceps Brachii ◽  
Neurological Impairment ◽  
Rehabilitation Robotics ◽  
Limiting Factor ◽  
Robot System ◽  
Physical Effort ◽  
Slow Progress ◽  
And Performance

Rehabilitation robotics is an emerging tool for motor recovery from various neurological impairments. However, balancing the human and robot contribution is an open problem. While the motor input can reduce fatigue, which is often a limiting factor of functional electrical stimulation (FES) exercises, too much assistance can slow progress. For a person with a neurological impairment, FES can assist by strategically contracting their muscle(s) to achieve a desired limb movement; however, feasibility can be limited due to factors such as subject comfort, muscle mass, unnatural muscle fiber recruitment, and stimulation saturation. Thus, motor assistance in addition to FES can be useful for prolonging exercise while still ensuring physical effort from the person. In this paper, FES is applied to the biceps brachii to perform biceps curls, and motor assistance is applied intermittently whenever the FES input reaches a pre-set comfort threshold. Exponential stability of the human–robot system is proven with a Lyapunov-like switched systems stability analysis. Experimental results from participants with neurological conditions demonstrate the feasibility and performance of the controller.

scholarly journals Role of calcium ions in the regulation of intramitochondrial metabolism. Properties of the Ca2+-sensitive dehydrogenases within intact uncoupled mitochondria from the white and brown adipose tissue of the rat

1980 ◽  
Vol 190 (1) ◽  
pp. 95-105 ◽  
Author(s):  
J G McCormack ◽  
R M Denton
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Isocitrate Dehydrogenase ◽  
Epididymal Adipose Tissue ◽  
Ionophore A23187 ◽  
Mitochondrial Inner Membrane ◽  
Brown Adipose ◽  
Oxoglutarate Dehydrogenase

1. Increasing concentrations of both Ca2+ and Sr2+ (generated by using EGTA buffers) resulted in 4-fold increases in the initial activity of pyruvate dehydrogenase within intact uncoupled mitochondria from rat epididymal adipose tissue incubated in the presence of the ionophore A23187, ATP, Mg2+ and oligomycin. The k0.5 values (concentrations required for half-maximal effects) for Ca2+ and Sr2+ were 0.54 and 7.1 microM respectively. In extracts of the mitochondria, pyruvate dehydrogenase phosphate phosphatase activity was stimulated about 4-fold by Ca2+ and Sr2+, with k0.5 values of 1.08 and 6.4 microM respectively. 2. NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase appeared to be rate-limiting in the oxidation of threo-Ds-isocitrate and oxoglutarate by uncoupled mitochondria from brown adipose tissue of cold-adapted rats. Ca2+ (and Sr2+) diminished the Km for the oxidation of both threo-Ds-isocitrate and oxoglutarate. The kinetic constants for these oxidations were very similar to those obtained for the activities of NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase in extracts of the mitochondria. In particular, the k0.5 values for Ca2+ were all in the range 0.2–1.6 microM and Sr2+ was found to mimic Ca2+, but with k0.5 values about 10 times greater. 3. Overall, the results of this study demonstrate that the activities of pyruvate dehydrogenase, NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase may all be increased by Ca2+ and Sr2+ within intact mitochondria. In all cases the k0.5 values are close to 1 and 10 microM respectively, as found for the separated enzymes. Experiments on brown-adipose-tissue mitochondria incubated in the presence of albumin suggest that it may be possible to use the sensitivity of the dehydrogenases to Ca2+ as a means of assessing the distribution of Ca2+ across the mitochondrial inner membrane.

De-stabilizing and training effects of foot orthoses in multiple sclerosis

2006 ◽  
Vol 12 (2) ◽  
pp. 219-226 ◽  
Author(s):  
G M Ramdharry ◽  
J F Marsden ◽  
B L Day ◽  
A J Thompson
Keyword(s):  
Multiple Sclerosis ◽  
Body Sway ◽  
Foot Orthoses ◽  
Balance Performance ◽  
Initial Session ◽  
Healthy Control ◽  
And Performance ◽  
Posterior Shift ◽  
And Training ◽  
Foot Alignment

This study evaluates the effects of dynamic foot orthoses (DFO) on walking and balance performance in people with multiple sclerosis (MS). Sixteen ambulant subjects with MS and ten age-matched healthy control subjects were studied on initial receipt of foot orthoses and after four weeks of daily wear. Walking speed, MS Walking Scale-12 (MSWS-12) and standing balance were assessed with and without orthoses at both these times. During standing, stance width and vision were varied, and performance was quantified using the velocity of the centre of pressure (COP), body sway velocity and the mean COP position relative to the shoe. People with MS walked slower (p<0.001) and showed increased sway when standing (p<0.001). At the first assessment, the foot orthoses caused an increase in sway and a medial and posterior shift of the COP position. At repeat measurement, the DFOs continued to increase sway compared to a shoe only condition. However, MS subjects reported an improvement in the MSWS-12 (p<0.05) and, compared to the initial session, showed decreased sway when eyes were closed both with and without DFOs. Dynamic foot orthoses may increase sway and change COP position by altering foot alignment and/or plantar afferent stimulation. Improvement in body sway over time may be an overall training effect of the DFOs, as MS subjects adapt to the initial de-stabilization.

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