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F A Sreter

Publications and source records attributed to F A Sreter.

At least 19 recordsLinked to original sources
PubMed1992

EU 4093 decreases intracellular [Ca2+] in skeletal muscle fibers from control and malignant hyperthermia-susceptible swine.

The mechanisms causing the malignant hyperthermia (MH) syndrome are related to a malfunction of intracellular Ca2+ homeostasis and can be prevented or reversed by dantrolene. EU 4093 (Azumolene, 1-[[[5-(4-bromophenyl)-2-oxyzolyl] methylene]amino]-2-4- imidazolidinedione) is a 30-fold more water-soluble analogue of dantrolene that is believed to have the same effects as dantrolene on the intracellular free Ca2+ concentration [( Ca2+]i) in skeletal muscle and that should have similar efficacy in treating and preventing the clinical manifestations of MH in response to a halothane/succinylcholine challenge. To test this hypothesis, experiments were carried out in four controls (Yorkshire) and eight MH-susceptible crossbreed swine (Poland China X Pietrain). The resting [Ca2+]i in normal muscle fibers measured by Ca(2+)-selective microelectrodes was 111 +/- 12 nM (mean +/- standard deviation, n = 30), whereas in the MH muscles the resting [Ca2+]i was 395 +/- 36 nM, (n = 28) (P = 0.0001). EU 4093 decreased [Ca2+]i in MH-susceptible skeletal muscle in a dose-related fashion from 207 to 38 nM after 0.5 to 2.0 mg/kg, respectively, and had a similar effect in control skeletal muscle (58 to 30 nM) after the same doses. In MH-susceptible swine, a dose of 2.0 mg/kg was successful in preventing any clinical signs of the MH syndrome during a subsequent halothane/succinylcholine challenge. A dose of 0.5 mg/kg was able to attenuate but not reverse the clinical signs of the MH syndrome after a halothane challenge, whereas a dose of 1.0 mg/kg was completely successful in reversing this effect in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine.

It is now well established that the pathophysiology of the malignant hyperthermia (MH) syndrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium [( Ca2+]i). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China X Pietrain). After determination of resting concentrations of [Ca2+]i and [Mg2+]i, each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+]i and [Mg2+]i were determined by means of ion-selective microelectrodes. The resting [Ca2+]i in normal muscle fibers was 0.11 +/- 0.01 microM (mean +/- SEM), whereas in the MH muscles the resting [Ca2+]i was 0.36 +/- 0.01 microM. In neither group was the resting [Ca2+]i modified by MgSO4. This cumulative dose of MgSO4 (100 mg/kg) was not able to prevent the induction of an MH episode by 2% halothane. Although MgSO4 did not directly decrease [Ca2+]i, it did attenuate the increase in [Ca2+]i associated with the syndrome from 7.29 +/- 0.43 microM in untreated animals to 0.84 +/- 0.03 microM in MgSO4 pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4 pretreatment. Baseline measurements of [Mg2+]i were not different in control and MH-susceptible muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Involvement of the 60 kDa phosphoprotein in the regulation of Ca2+ release from sarcoplasmic reticulum of normal and malignant hyperthermia susceptible pig muscles.

Junctional sarcoplasmic reticulum (SR) vesicles isolated from back muscles of normal and malignant hyperthermia susceptible (MHS) pigs were phosphorylated by addition of MgATP in the presence of 5 mM Ca2+ and 1 microM calmodulin (CaM). The major site of phosphorylation was a 60 kDa protein both in normal and MHS SR. The maximal amount of phosphorylation in MHS SR (5 pmol P/mg SR) was significantly lower than that in the normal SR (12 pmol P/mg SR). The phosphorylated 60 kDa protein was spontaneously dephosphorylated both in normal and MHS SR. Ca2+ release from the passively loaded SR was induced by a Ca2+-jump, and monitored by stopped-flow fluorometry using chlorotetracycline. In the absence of preincubation with MgATP, no significant difference was found in any of the kinetic parameters of Ca2+ release between normal and MHS SR. Upon addition of 20 microM MgATP to the passively loaded SR to phosphorylate the 60 kDa protein, the initial rate of Ca2+ release in normal SR significantly decreased from 659 +/- 102 to 361 +/- 105 nmol Ca2+/mg SR per s, whereas in MHS SR the rate decreased from 749 +/- 124 to 652 +/- 179 nmol Ca2+/mg SR per s. Addition of 20 microM adenosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppA) did not significantly alter the initial rate of Ca2+ release both in normal and MHS SR. These results suggest that the previously reported higher Ca2+ release rate in MHS SR (Kim et al. (1984) Biochim. Biophys. Acta 775, 320-327) is at least partly due to the reduced extent of the Ca2+/CaM-dependent phosphorylation of the 60 kDa protein. Two-dimensional gel electrophoresis study showed that amount of a protein with Mr = 55,000 was significantly lower in MHS SR than in normal SR suggesting that the abnormally lower amount of 55 kDa protein would cause the lower amount of phosphorylation of the 60 kDa protein in MHS SR.

Animals↗
PubMed1988

Myoplasmic free [Ca2+] during a malignant hyperthermia episode in swine.

Malignant hyperthermia (MH) is a genetic syndrome usually initiated by exposure to volatile anesthetic agents or depolarizing neuromuscular blocking agents. We have used Ca2+-selective microelectrodes to measure in vivo the intracellular ionized calcium ([Ca2+]i) in skeletal muscle fibers of MH-susceptible swines before and during hyperthermic episodes and also after dantrolene administration. The animals were anesthetized with thiopental and fentanyl and maintained with a mixture of nitrous oxide (66%) and oxygen (34%). The malignant hyperthermic episode was triggered by exposure to halothane. Determinations of [Ca2+]i during the episode show an increase from 0.44 +/- 0.01 microM +/- SEM, n = 20) to 8.44 +/- 0.68 microM (mean +/- SEM, n = 10). Administration of dantrolene (2 mg/kg) during the hyperthermic episode reduces [Ca2+]i to 0.17 + 0.01 microM (mean +/- SEM, n = 10) and reverses the clinical symptoms. These results show that the MH episode is associated with an increase in the myoplasmic free Ca2+ concentration and that the therapeutic effect of dantrolene is related to a decrease in [Ca2+]i.

Animals↗
PubMed1987

Changes in intracellular ionized Ca concentration associated with muscle fiber type transformation.

Since increased muscle activity, which results in fast-slow fiber transformation, is associated with increases in sarcoplasmic Ca2+ concentration ([Ca2+]i), it seemed of interest to study the level of [Ca2+] after cessation of stimulation in fibers of the extensor digitorum longus muscle chronically stimulated (8 Hz). [Ca2+]i was measured in individual fibers with a Ca2+-sensitive electrode after subtracting the membrane potential, measured simultaneously from the potential of the Ca2+ electrode. During the first 14 days of stimulation, [Ca2+]i increased from approximately 0.1 to 0.5 microM and declined in approximately 3 wk to a value slightly higher than the initial one. The rise and decline of [Ca2+]i was preceded by a transient increase in total calcium. If stimulation was terminated after 7-8 wk when an essentially complete fast-to-slow transformation had taken place, a subsequent rest period led to a reverse slow-to-fast transformation, which was also preceded by a transient increase of [Ca2+]i reaching a peak at day 5 of rest. Unstimulated fast and slow fibers and fully transformed fibers do not differ in their [Ca2+] levels; thus it appears that the transformation process itself is accompanied, particularly in its earlier stages, by elevated [Ca2+]i levels. Elucidation of the relation between changes in Ca2+ and changes in gene expression will require further work.

Adenosine Triphosphatases↗
PubMed1985

Inhibitors of Ca2+ release from the isolated sarcoplasmic reticulum. II. The effects of dantrolene on Ca2+ release induced by caffeine, Ca2+ and depolarization.

The effects of dantrolene, which is a known muscle relaxant, on Ca2+ release from the isolated sarcoplasmic reticulum induced by several different methods [1) addition of caffeine, (2) Ca2+ jump, and (3) membrane-depolarization produced by choline chloride replacement of potassium gluconate) were investigated. Dantrolene inhibited caffeine-induced Ca2+ release with C1/2 = 2.5 microM, whereas there was no effect on Ca2+ release induced by a Ca2+ jump. The amount of Ca2+ released by depolarization was reduced if Ca2+ release was triggered in an earlier phase of the steady state of Ca2+ uptake (time elapsed between the addition of ATP and the triggering of Ca2+ release, tATP less than 4 min); while, if triggered in a latter phase (tATP greater than 4 min) dantrolene enhanced depolarization-induced Ca2+ release. C1/2 for the inhibition and that for enhancement of depolarization-induced Ca2+ release were 1.0 and 0.3 microM, respectively. These results suggest that dantrolene affects several different steps of the mechanism by which Ca2+ release is triggered. The sarcoplasmic reticulum and T-tubule membrane fractions had 7.9 nmol dantrolene-binding sites/mg (Kassoc = 1.0 X 10(5) M-1) and 21.0 nmol/mg (Kassoc = 1.1 X 10(5) M-1), respectively. The time-course of dantrolene binding to sarcoplasmic reticulum was monophasic, while that to T-tubules was biphasic.

Animals↗
PubMed1984

Kinetic studies of Ca2+ release from sarcoplasmic reticulum of normal and malignant hyperthermia susceptible pig muscles.

The time-course of Ca2+ release from sarcoplasmic reticulum isolated from muscles of normal pigs and those of pigs susceptible to malignant hyperthermia were investigated using stopped-flow spectrophotometry and arsenazo III as a Ca2+ indicator. Several methods were used to trigger Ca2+ release: (a) addition of halothane (e.g., 0.2 mM); (b) an increase of extravesicular Ca2+ concentration ([Ca2+0]); (c) a combination of (a) and (b), and (d) replacement of ions (potassium gluconate with choline chloride) to produce membrane depolarization. The initial rates of Ca2+ release induced by either halothane or Ca2+ alone, or both, are at least 70% higher in malignant hyperthermic sarcoplasmic reticulum than in normal. The amount of Ca2+ released by halothane at low [Ca2+0] in malignant hyperthermic sarcoplasmic reticulum is about twice as large as in normal sarcoplasmic reticulum. Membrane depolarization led to biphasic Ca2+ release in both malignant hyperthermic and normal sarcoplasmic reticulum, the rate constant of the rapid phase of Ca2+ release induced by membrane depolarization being significantly higher in malignant hyperthermic sarcoplasmic reticulum (k = 83 s-1) than in normal (k = 37 s-1). Thus, all types of Ca2+ release investigated (a, b, c and d) have higher rates in malignant hyperthermic sarcoplasmic reticulum than normal sarcoplasmic reticulum. These results suggest that the putative Ca2+ release channels located in the sarcoplasmic reticulum are altered in malignant hyperthermic sarcoplasmic reticulum.

Animals↗
PubMed1983

Correlation between protein phenotype and gene expression in adult rabbit fast twitch muscles undergoing a fast to slow fiber transformation in response to electrical stimulation in vivo.

In this report we have defined three distinct stages of the fast to slow transformation of muscle in terms of the myosin isoenzyme pattern in a non-denaturing gel system. In phase I a rearrangement of fast isoenzymes with no increase in slow isoforms took place. Phase II is characterised by a complex pattern of fast and slow isoenzymes and of isoenzymes of intermediate mobility. Phase III shows full conversion to the slow isoform with residual traces of fast and intermediate components. Changes in myosin light chains, as revealed by two dimensional gel analysis, showed good correlation with their corresponding mRNAs as determined by translation of extracted total RNA in a nuclease treated reticulocyte lysate cell-free system. This suggests that in the fast to slow transformation gene expression is regulated at the level of transcription.

Animals↗
PubMed1982

Changes in myosin isozyme distribution induced by low doses of isoproterenol.

The Ca2+-activated myosin ATPase activity in isoproterenol-induced hypertrophied left ventricle increased by 20-30% while in Goldblatt rats hypertrophy occurred with a decreased myosin ATPase activity. In non-dissociating (pyrophosphate) gel electrophoresis isoproterenol treatment showed decreased V2 and V3 myosin isozymes; at the higher dose of isoproterenol (0.5 mg/kg body weight) only V1 was present. In contrast a shift toward the V3 isozyme is present in the ventricles of Goldblatt rats. One group of rats was treated with toxic doses of digitoxin: no hypertrophy occurred but there was a disappearance of V1 and V2 isozymes and a 50% decrease in Ca2+-activated ATPase activity. Thus low doses of isoproterenol produce hypertrophy with an isozyme pattern similar to that found in young (approximately 4-6 weeks old) rats. The results with digitoxin show that shifts in the cardiac isozyme distribution can occur without hypertrophy.

Adenosine Triphosphatases↗
PubMed1976

Characteristics of myosin in nemaline myopathy.

Electron-microscopic, morphometric, histochemical and biochemical studies were carried out on muscle biopsies from a patient with the characteristic clinical and pathological findings of nemaline myopathy. The mean fiber diameter was decreased, and the vastus lateralis muscle biopsy consisted exclusively of slow twitch (Type I) fibers. Quantitative biochemical investigations revealed significantly low calcium uptake and ATPase activity of the fragmented sarcoplasmic reticulum and decreased myosin ATPase activity. The electrophoretogram of myosin showed an abnormality in the light chain pattern which could not be explained by a disproportion of normal fiber types.

Adult↗