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At least 325 records · Page 18Linked to original sources
PubMed1986

Nucleotide exchange between cytosolic ATP and F-actin-bound ADP may be a major energy-utilizing process in unstimulated platelets.

About 40% of the cytosolic ADP of human platelets is tightly bound to protein and the complex is precipitated from the cells by 43% ethanol. We show here that this ADP is bound to F-actin by three criteria (a) copurification with F-actin, (b) specific extraction with water and (c) by specific interaction with DNase I. Platelets contain 0.3 mumol/10(11) cells of this F-actin--ADP complex compared to the total actin content of 0.8 mumol/10(11) cells, which is consistent with the view that actin is maintained in different pools (F-actin--ADP, profilactin, G-actin). In intact platelets the F-actin-bound ADP turns over rapidly and we have determined a turnover rate at 37 degrees C of 0.1 +/- 0.025 s-1 by using a double-labelling procedure. This rapid turnover indicates that F-actin in intact platelets is in a very dynamic state, which may be necessary for rapid responses to stimuli. If it is assumed that the source of the ADP bound to F-actin is cytosolic ATP, the turnover of F-actin ADP measured represents an ATP-consuming process that would account for up to 50% of total ATP consumption in resting platelets.

Actins↗
PubMed1987

Turnover of the phosphomonoester groups of polyphosphoinositol lipids in unstimulated human platelets.

The metabolic activity of the polyphosphoinositol lipids in unstimulated human platelets was studied by short-term labelling with [32P]Pi, by replacement of [32P]Pi from pre-labelled platelets with unlabelled phosphate, and by depriving the cells of metabolic ATP. Under short-term labelling conditions, the 4- and 5-phosphate groups of phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] had the same specific 32P radioactivity as the gamma-phosphate of metabolic ATP. The specific 32P radioactivity of the 1-phosphates of phosphatidylinositol, PtdIns4P and PtdIns(4,5)P2 was similar, but only 4-13% compared to that of the ATP-gamma-phosphate. When [32P]Pi pre-labelled platelets were incubated with up to 25 mM of unlabelled phosphate, the displacement of the 32P label from PtdIns4P, PtdIns(4,5)P2 and metabolic ATP followed similar kinetics. Inhibition of ATP regeneration in platelets pre-labelled with [32P]Pi resulted in a rapid fall in metabolic ATP with a much slower fall in [32P]PtdIns(4,5)P2, whereas [32P]PtdIns4P increased initially. However, ATP turnover was not abolished, as indicated by the marked (25% of the control) incorporation of extracellular [32P]Pi into PtdIns4P and PtdIns(4,5)P2 in metabolically inhibited platelets. This low phosphate turnover may explain the relative resistance of PtdIns4P and PtdIns(4,5)P2 to metabolic inhibition. We conclude that PtdIns4P and PtdIns(4,5)P2 are present as a single metabolic pool in human platelets. Turnover of the 4- and 5-phosphates of PtdIns4P and PtdIns(4,5)P2 in unstimulated platelets is as rapid as that of the gamma-phosphate of metabolic ATP, and accounts for about 7% of basal ATP consumption.

Adenosine Diphosphate↗
PubMed1987

The effect of kallikrein on spermatozoal ATP and other semen parameters.

Kallikrein promotes the release of kinins, which have been shown in in vitro studies to improve motility, viability and metabolism in human spermatozoa. The effects of kallikrein therapy on 25 males attending an infertility clinic was assessed, regarding endogenous spermatozoal ATP content, as well as other semen parameters. Thirteen of the 25 patients showed an improvement in either count, morphology, motility, viability, or a combination of these, after 3 months Kallikrein therapy. ATP levels in responders dropped by 58.8% (p less than 0.001). In nonresponders ATP levels did not change significantly. This indicates that improvement in spermatozoal parameters corresponds with increased ATP consumption, following Kallikrein therapy.

Adenosine Triphosphate↗
PubMed1997

Energetic cost of activation processes during contraction of swine arterial smooth muscle.

1. The objective of this study was to partition the increase in ATP consumption during contraction of swine carotid arterial smooth muscle estimated from suprabasal oxygen consumption (suprabasal JO2) and lactate release (Jlactate) into a component associated with cross-bridge cycling (JX) and one reflecting activation (JA). 2. Two experimental approaches-varying length under constant activation, and varying activation at a long length (1.8 times the optimal length for force development (Lo)) where force generation is minimal-revealed a linear dependence of JO2 and activation energy (JA) on cross-bridge phosphorylation. Protocols inducing a large increase in myosin regulatory light chain (MRLC) phosphorylation at 1.8 Lo resulted in significant elevations of JO2 and marked reductions in the economy of force maintenance. Our evidence suggests that this is primarily due to the increased cost of cross-bridge phosphorylation. 3. The extrapolated estimate of JA during maximal K(+)-induced depolarization made by varying length was 16%, while at 1.8 Lo it was 33% of the suprabasal JO2 at Lo. Calculated activation energies ranged from 17 to 45% of the suprabasal JO2 at Lo and from 72 to 87% of the suprabasal JO2 at 1.8 Lo under stimulation conditions that varied steady-state MRLC phosphorylation from 15 to 50%. 4. The results suggest that the kinetics of cross-bridge phosphorylation-dephosphorylation can rival those of cross-bridge cycling during isometric contractions in swine arterial smooth muscle.

Adenosine Triphosphate↗
PubMed1989

Interrelationships between glucose metabolism, energy state, and the cytosolic free calcium concentration in cortical synaptosomes from the guinea pig.

The stoichiometries of glycolysis and pyruvate oxidation were determined in cortical synaptosomes under varying rates of ATP consumption. Glycolysis was measured by using D-3-[3H]glucose as a marker and pyruvate oxidation by using D-3,4-[14C]glucose, which has to be metabolized to 1-[14C]pyruvate before being decarboxylated by the pyruvate dehydrogenase complex of intrasynaptosomal mitochondria. Cytosolic free Ca2+ concentration [( Ca2+]c) was determined in parallel and was manipulated by using EGTA in the incubation. The results show that in nonstimulated synaptosomes glycolysis and pyruvate oxidation are tightly coupled and stoichiometric. In the absence of Ca2+, when [Ca2+]c drops from 260 nM to 40 nM, glucose utilization increases, following the increase in energy demand, which has been shown to be due to elevated Na+ cycling. KCl depolarization, veratridine, and a mitochondrial uncoupler, carbonyl cyanide m-chlorophenylhydrazone, all stimulate glycolysis and pyruvate oxidation stoichiometrically, independently of the presence of external Ca2+. A rise in [Ca2+]c, therefore, is not required to regulate mitochondrial pyruvate metabolism. It is concluded that synaptosomes exhibit a high degree of respiratory control, that they rely on glucose oxidation for their energetics, and that stimulation of energy production can be achieved independently of changes in [Ca2+]c.

Adenosine Triphosphate↗
PubMed2006

Functional consequence of mutation in rat cardiac troponin T is affected differently by myosin heavy chain isoforms.

Cardiac troponin T (cTnT) is an essential component of the thin filament regulatory unit (RU) that regulates Ca2+ activation of tension in the heart muscle. Because there is coupling between the RU and myosin crossbridges, the functional outcome of cardiomyopathy-related mutations in cTnT may be modified by the type of myosin heavy chain (MHC) isoform. Ca2+ activation of tension and ATPase activity were measured in muscle fibres from normal rat hearts containing alpha-MHC isoform and propylthiouracil (PTU)-treated rat hearts containing beta-MHC isoform. Muscle fibres from normal and PTU-treated rat hearts were reconstituted with two different mutations in rat cTnT; the deletion of Glu162 (cTnT(E162DEL)) and the deletion of Lys211 (cTnT(K211DEL)). Alpha-MHC and beta-MHC isoforms had contrasting impact on tension-dependent ATP consumption (tension cost) in cTnT(E162DEL) and cTnT(K211DEL) reconstituted muscle fibres. Significant increases in tension cost in alpha-MHC-containing muscle fibres corresponded to 17% (P < 0.01) and 23% (P < 0.001) when reconstituted with cTnT(E162DEL) and cTnT(K211DEL), respectively. In contrast, tension cost decreased when these two cTnT mutants were reconstituted in muscle fibres containing beta-MHC; by approximately 24% (P < 0.05) when reconstituted with cTnT(E162DEL) and by approximately 17% (P = 0.09) when reconstituted with cTnT(K211DEL). Such differences in tension cost were substantiated by the mechano-dynamic analysis of cTnT mutant reconstituted muscle fibres from normal and PTU-treated rat hearts. Our observation demonstrates that qualitative changes in MHC isoform alters the nature of cardiac myofilament dysfunction induced by mutations in cTnT.

Amino Acid Substitution↗
PubMed2006

In vivo ATP production during free-flow and ischaemic muscle contractions in humans.

The aim of this study was to determine how ATP synthesis and contractility in vivo are altered by ischaemia in working human skeletal muscle. The hypotheses were: (1) glycolytic flux would be higher during ischaemic (ISC) compared to free-flow (FF) muscle contractions, in compensation for reduced oxidative ATP synthesis, and (2) ischaemic muscle fatigue would be related to the accumulation of inhibitory metabolic by-products rather than to the phosphorylation potential ([ATP]/[ADP][P(i)]) of the muscle. Twelve healthy adults (6 men, 6 women) performed six intermittent maximal isometric contractions of the ankle dorsiflexors (12 s contract, 12 s relax), once with intact blood flow and once with local ischaemia by thigh cuff inflation to 220 Torr. Intracellular phosphorous metabolites and pH were measured non-invasively with magnetic resonance spectroscopy, and rates of ATP synthesis through oxidative phosphorylation, anaerobic glycolysis, and the creatine kinase reaction were determined. The force-time integral declined more during ISC (66 +/- 3% initial) than FF (75 +/- 2% initial, P = 0.002), indicating greater fatigue in ISC. [ATP] was preserved in both protocols, indicating matching of ATP production and use under both conditions. Glycolytic flux (mm s(-1)) was similar during FF and ISC (P = 0.16). Total ATP synthesis rate was lower during ISC, despite adjustment for the greater muscle fatigue in this condition (P < 0.001). Fatigue was linearly associated with diprotonated inorganic phosphate (FF r = 0.94 +/- 0.01, ISC r = 0.92 +/- 0.02), but not phosphorylation potential. These data provide novel evidence that ATP supply and demand in vivo are balanced in human skeletal muscle during ischaemic work, not through higher glycolytic flux, but rather through increased metabolic economy and decreased rates of ATP consumption as fatigue ensues.

Adenosine Triphosphate↗
PubMed2001

Effect of poly(ADP-ribose) polymerase inhibitors on the ischemia-reperfusion-induced oxidative cell damage and mitochondrial metabolism in Langendorff heart perfusion system.

Ischemia-reperfusion induces reactive oxygen species (ROS) formation, and ROS lead to cardiac dysfunction, in part, via the activation of the nuclear poly(ADP-ribose) polymerase (PARP, called also PARS and ADP-RT). ROS and peroxynitrite induce single-strand DNA break formation and PARP activation, resulting in NAD(+) and ATP depletion, which can lead to cell death. Although protection of cardiac muscle by PARP inhibitors can be explained by their attenuating effect on NAD(+) and ATP depletion, there are data indicating that PARP inhibitors also protect mitochondria from oxidant-induced injury. Studying cardiac energy metabolism in Langendorff heart perfusion system by (31)P NMR, we found that PARP inhibitors (3-aminobenzamide, nicotinamide, BGP-15, and 4-hydroxyquinazoline) improved the recovery of high-energy phosphates (ATP, creatine phosphate) and accelerated the reutilization of inorganic phosphate formed during the ischemic period, showing that PARP inhibitors facilitate the faster and more complete recovery of the energy production. Furthermore, PARP inhibitors significantly decrease the ischemia-reperfusion-induced increase of lipid peroxidation, protein oxidation, single-strand DNA breaks, and the inactivation of respiratory complexes, which indicate a decreased mitochondrial ROS production in the reperfusion period. Surprisingly, PARP inhibitors, but not the chemically similar 3-aminobenzoic acid, prevented the H(2)O(2)-induced inactivation of cytochrome oxidase in isolated heart mitochondria, suggesting the presence of an additional mitochondrial target for PARP inhibitors. Therefore, PARP inhibitors, in addition to their important primary effect of decreasing the activity of nuclear PARP and decreasing NAD(+) and ATP consumption, reduce ischemia-reperfusion-induced endogenous ROS production and protect the respiratory complexes from ROS induced inactivation, providing an additional mechanism by which they can protect heart from oxidative damages.

Aminobenzoates↗
PubMed2005

The latch-bridge hypothesis of smooth muscle contraction.

In contrast to striated muscle, both normalized force and shortening velocities are regulated functions of cross-bridge phosphorylation in smooth muscle. Physiologically this is manifested as relatively fast rates of contraction associated with transiently high levels of cross-bridge phosphorylation. In sustained contractions, Ca2+, cross-bridge phosphorylation, and ATP consumption rates fall, a phenomenon termed "latch". This review focuses on the Hai and Murphy (1988a) model that predicted the highly non-linear dependence of force on phosphorylation and a directly proportional dependence of shortening velocity on phosphorylation. This model hypothesized that (i) cross-bridge phosphorylation was obligatory for cross-bridge attachment, but also that (ii) dephosphorylation of an attached cross-bridge reduced its detachment rate. The resulting variety of cross-bridge cycles as predicted by the model could explain the observed dependencies of force and velocity on cross-bridge phosphorylation. New evidence supports modifications for more general applicability. First, myosin light chain phosphatase activity is regulated. Activation of myosin phosphatase is best demonstrated with inhibitory regulatory mechanisms acting via nitric oxide. The second modification of the model incorporates cooperativity in cross-bridge attachment to predict improved data on the dependence of force on phosphorylation. The molecular basis for cooperativity is unknown, but may involve thin filament proteins absent in striated muscle.

Animals↗
PubMed1983

Energy metabolism of preimplantation mammalian blastocysts.

We have measured the relative contributions of glycolytic and oxidative energy production pathways of metabolism in rabbit and mouse preimplantation blastocysts. We have further studied the relationship between these pathways and active transepithelial Na+ transport. Our results show that over 85% of all ATP production arises from mitochondrial respiration. By using amphotericin B to increase the Na+ permeability of the apical (or uterine-facing) membrane of the blastocyst, we have determined that the ratio of ouabain-sensitive Na+ influx to ATP consumption is 3. Based on the measurements of ouabain-sensitive Na+ influx across blastocysts incubated in glucose-containing medium, only 6% of the total energy consumption of the embryo is used for active transepithelial Na+ transport.

Adenosine Triphosphate↗
PubMed1988

Regulation of shortening velocity by cross-bridge phosphorylation in smooth muscle.

We have proposed a model that incorporates a dephosphorylated "latch bridge" to explain the mechanics and energetics of smooth muscle. Cross-bridge phosphorylation is proposed as a prerequisite for cross-bridge attachment and rapid cycling. Features of the model are 1) myosin light chain kinase and phosphatase can act on both free and attached cross bridges, 2) dephosphorylation of an attached phosphorylated cross bridge produces a noncycling "latch bridge," and 3) latch bridges have a slow detachment rate. This model quantitatively predicts the latch state: stress maintenance with reduced phosphorylation, cross-bridge cycling rates, and ATP consumption. In this study, we adapted A. F. Huxley's formulation of crossbridge cycling (A. F. Huxley, Progr. Biophys. Mol. Biol. 7: 255-318, 1957) to the latch-bridge model to predict the relationship between isotonic shortening velocity and phosphorylation. The model successfully predicted the linear dependence of maximum shortening velocity at zero external load (V0) on phosphorylation, as well as the family of stress-velocity curves determined at different times during a contraction when phosphorylation values varied. The model implies that it is unnecessary to invoke an internal load or multiple regulatory mechanisms to explain regulation of V0 in smooth muscle.

Algorithms↗
PubMed1990

Latch-bridge model in smooth muscle: [Ca2+]i can quantitatively predict stress.

Ca2+ concentration ([Ca2+])-dependent cross-bridge phosphorylation by myosin light chain kinase is postulated to be the primary regulator of stress development in smooth muscle. A four-state model of cross-bridge function, regulated only by [Ca2+]-dependent changes in myosin kinase activity, has been proposed to explain contraction and the latch state of smooth muscle (high force with reduced cross-bridge cycling and ATP consumption). A key test of this model is to determine whether changes in myoplasmic [Ca2+], per se, can quantitatively predict changes in myosin kinase activity, cross-bridge phosphorylation, and therefore force production. We find that changes in aequorin-estimated myoplasmic [Ca2+] can quantitatively predict the time course of phosphorylation and isometric stress production in response to stimulation with histamine and angiotensin II and during adenosine 3',5'-cyclic monophosphate-mediated relaxation when [Ca2+] is not changing rapidly. These results suggest that changes in myoplasmic [Ca2+] and activation of myosin light chain kinase may be sufficient to explain both contraction and relaxation of agonist stimulated swine carotid arterial smooth muscle.

Animals↗
PubMed2004

Depressed cardiac tension cost in experimental diabetes is due to altered myosin heavy chain isoform expression.

Cardiac disease in diabetes presents as impaired left ventricular contraction and relaxation; however, the mechanisms underlying contractile protein dysfunction during the progression of disease are unknown. Accordingly, we assessed Ca(2+)-dependent tension development and tension-dependent ATP consumption (tension cost) in a rat model early (6 wk) and late (12 wk) after the onset of diabetes (50 mg/kg iv streptozotocin) using mechanical force- and enzyme-coupled UV absorbance measurements. Myofilament Ca(2+) sensitivity and maximal tension were unchanged between groups at either time point. Cross-bridge cycling rate was significantly decreased in diabetes, as indexed by tension cost (early control 5.4 +/- 0.4 and early diabetes 4.2 +/- 0.3; and late control 6.0 +/- 0.2 and late diabetes 4.2 +/- 0.2; P < 0.05). Because rodent models of cardiac disease are confounded by altered myosin isoform distribution, myosin content was determined by SDS-PAGE and densitometry. The cardiac content of alpha-myosin in diabetes was decreased to 41% +/- 4.1 at 6 wk and 32.5% +/- 2.9 at 12 wk of diabetes (early control 77.8% +/- 3.3 and late control 73.6% +/- 2.5). Separate control experiments demonstrated a linear decrease in tension cost with decreased alpha-myosin content. Given this, the depression of tension cost in this rodent model of diabetes could be fully explained by the altered myosin isoform distribution.

Animals↗
PubMed1987

Action potential duration in ventricular muscle during selective metabolic block.

We have examined whether maintenance of the cardiac action potential duration depends exclusively on energy from glycolysis. Oxidative phosphorylation in guinea pig papillary muscles was inhibited by superfusion with hypoxic solutions. After 60 min in 50 mM glucose solution, the action potential duration was 85% of aerobic control, but ATP content was only 25%; after 60 min in 0 mM glucose, both the duration and ATP content had declined to 15% control. When the glucose concentration of hypoxic solution was raised from 0 to 50 mM, there was nearly full recovery of the action potential duration but ATP only increased to about 25% control. We attribute action potential shortening during metabolic inhibition to suppression of calcium current and activation of potassium current; the latter are graded in intensity and expressed only at low ATP. When normoxic muscle was treated with 20 mM 2-deoxy-D-glucose (2-DG) to inhibit glycolysis, there was an early transient shortening of the action potential. This was attributed to ATP consumption related to early rapid 2-DG influx and phosphorylation. After the transient, the action potential duration was maintained for several hours in oxygenated 2-DG solution. The duration was also maintained in oxygenated muscle depleted of glycolytic substrate. Thus we found no evidence of an exclusive relation between action potential duration and glycolysis.

Acetates↗
PubMed1998

Effect of ANG II on pHi, [Ca2+]i, and contraction in rabbit ventricular myocytes from infarcted hearts.

In this study we examined Na+/H+ exchange activity, Ca2+ transients, and contractility in rabbit ventricular myocytes isolated from normal and chronically (8-12 wk) infarcted left ventricles. Myocytes from infarcted hearts (post-MI myocytes) were isolated from the peri-infarcted region of the left ventricle. Intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were measured with the fluorescent pH indicators seminaphthorhodafluor 1 and fluo 3, respectively, and contractility was assessed from changes in cell shortening during field stimulation. Experiments were performed at extracellular pH 7. 4 in the presence and absence (HEPES buffer) of CO2 and HCO-3. Our findings demonstrate that 1) myocytes after myocardial infarction (post-MI) were significantly larger than normal, 2) post-MI hypertrophy was not accompanied by changes in non-CO2 intracellular buffering power, 3) post-MI hypertrophy did not significantly affect the ability of Na+/H+ exchange to mediate pHi recovery from intracellular acidosis, 4) the stimulatory effect of ANG II (100 nM) on Na+/H+ exchange was significantly reduced in post-MI myocytes, 5) in HCO-3-buffered solutions, ANG II did not significantly stimulate pHi recovery from acidosis in post-MI myocytes, 6) the angiotensin AT1 receptor mediates the stimulatory action of ANG II on Na+/H+ exchange in normal and post-MI myocytes, and 7) the stimulatory effect of ANG II on the Ca2+ transient and contraction was blunted in post-MI myocytes bathed in HEPES-buffered solution. A suppressed ventricular responsiveness to ANG II may be beneficial in the intact myocardium by attenuating ATP consumption and by reducing intracellular Na+ accumulation during ischemia-reperfusion.

Angiotensin II↗
PubMed2001

Ca(2+) activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T.

The functional consequences of the R92Q mutation in cardiac troponin T (cTnT), linked to familial hypertrophic cardiomyopathy in humans, are not well understood. We have studied steady- and pre-steady-state mechanical activity of detergent-skinned fiber bundles from a transgenic (TG) mouse model in which 67% of the total cTnT in the heart was replaced by the R92Q mutant cTnT. TG fibers were more sensitive to Ca(2+) than nontransgenic (NTG) fibers [negative logarithm of half maximally activating molar Ca(2+) (pCa(50)) = 5.84 +/- 0.01 and 6.12 +/- 0.01 for NTG and TG fibers, respectively]. The shift in pCa(50) caused by increasing the sarcomere length from 1.9 to 2.3 microm was significantly higher for TG than for NTG fibers (DeltapCa(50) = 0.13 +/- 0.01 and 0.29 +/- 0.02 for NTG and TG fibers, respectively). The relationships between rate of ATP consumption and steady-state isometric tension were linear, and the slopes were the same in NTG and TG fibers. Rate of tension redevelopment was more sensitive to Ca(2+) in TG than in NTG fibers (pCa(50) = 5.71 +/- 0.02 and 6.07 +/- 0.02 for NTG and TG fibers, respectively). We concluded that overall cross-bridge cycling kinetics are not altered by the R92Q mutation but that altered troponin-tropomyosin interactions could be responsible for the increase in myofilament Ca(2+) sensitivity in TG myofilaments.

Acidosis↗
PubMed2001

Effects of kappa-opioid receptor activation on myocardium.

Kappa-opioid receptor stimulation of the heart transiently increases twitch amplitude and decreases Ca2+-dependent actomyosin Mg2+-ATPase activity through an undetermined mechanism. One purpose of the present study was to determine if the increase in twitch amplitude is due to changes in myofilament Ca2+ sensitivity. We also wanted to determine if kappa-opioid receptor activation alters maximum actin-myosin ATPase activity and Ca2+ sensitivity of tension in a way consistent with protein kinase A or protein kinase C (PKC) action. Rat hearts were treated with U50,488H (a kappa-opioid receptor agonist), phenylephrine plus propranolol (alpha-adrenergic receptor stimulation), isoproterenol (a beta-adrenergic receptor agonist), or phorbol 12-myristate 13-acetate (PMA, receptor independent activator of PKC) or were untreated (control), and myofibrils were isolated. U50,488H, phenylephrine plus propranolol, and PMA all decreased maximum Ca2+-dependent actomyosin Mg2+-ATPase activity, whereas isoproterenol treatment increased maximum Ca2+-dependent actomyosin Mg2+- ATPase activity. Untreated myofibrils exposed to exogenous PKC-epsilon, but not PKC-delta, decreased maximum actomyosin Mg2+-ATPase activity. Langendorff-perfused hearts treated with U50,488H, phenylephrine plus propranolol, or isoproterenol had significantly higher ventricular ATP levels compared with control hearts. PKC inhibitors abolished the effects of U50,488H on Ca2+-dependent actomyosin Mg2+-ATPase activity and myocardial ATP levels. U50,488H and PMA treatment of isolated ventricular myocytes increased Ca2+ sensitivity of isometric tension compared with control myocytes at pH 7.0. The U50,488H-dependent increase in Ca2+ sensitivity of tension was retained at pH 6.6. Together, these findings are consistent with the hypotheses that 1) the positive inotropy associated with kappa-opioid receptor activation may be due in part to a PKC-mediated increase in myofilament Ca2+-sensitivity of tension and 2) the kappa-opioid receptor-PKC pathway is a modulator of myocardial energy status through reduction of actomyosin ATP consumption.

Analgesics, Non-Narcotic↗
PubMed1988

Energy cost and fatigue during intermittent electrical stimulation of human skeletal muscle.

Force generation and ATP utilization under anaerobic conditions were studied in the quadriceps femoris muscle of six volunteers. Electrical stimulation (20 Hz) was used to produce contractions with a duration of 0.8 s in one leg and contractions with a duration of 3.2 s in the other leg. The two procedures were designed to give the same total contraction time of 51 s and used the same number of stimulation pulses. Muscle biopsies were taken at rest and after 22 and 51 s of work and analyzed for ATP, phosphocreatine, and glucolytic intermediates. The results were compared with previous studies on continuous and intermittent stimulation. Fatigue developed significantly faster with contractions of short duration, and the energy cost was higher. Since force at the end of stimulation had a negative correlation to ATP utilization, there is no indication that the energy resources limit force generation. By comparison of stimulations producing the same amount of isometric work but with a different number of contractions, we estimate that the energy cost for activation and relaxation of a 1-s contraction is approximately 37% of the total ATP consumption.

Adenosine Diphosphate↗