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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Indirect and direct twitch (0.1-Hz) stimulation of the rat phrenic nerve-diaphragm disclosed that the inhibitory effect of HgCl2, 3.7 x 10(-5) M, on the neuromuscular transmission and in the muscle cell, was accelerated by 10-sec periods of 50-Hz tetanic stimulation every 10 min. This activity-dependent enhancement suggested an inhibitory mechanism of HgCl2 related to the development of fatigue, like membrane depolarization or decreased excitability, decreased availability of transmitter, or interference with the factors controlling excitation-secretion coupling of the nerve terminal, i.e. (Ca2+)0 or (Ca2+)i, and excitation-contraction coupling in the muscle cell, i.e., (Ca2+)i. 2. During both indirect and direct stimulation, HgCl2-induced inhibition was enhanced markedly by pretreatment with caffeine, which releases Ca2+ from endoplasmic and sarcoplasmic reticulum in the nerve terminal and muscle cell, respectively. This caffeine-induced enhancement was completely antagonized by dantrolene, which inhibits the caffeine-induced release. However, dantrolene alone did not antagonize the HgCl2-induced inhibition. 3. Since caffeine depletes the intracellular Ca2+ stores of the smooth endoplasmic reticulum, HgCl2 probably inhibits by binding to SH groups of transport proteins conveying the messenger function of (Ca2+)i. In the muscle cell this leads to inhibition of contraction. In the nerve terminal, an additional enhancement of the HgCl2-induced inhibition, by inhibiting reuptake of choline by TEA and tetanic stimulation, suggested that HgCl2 inhibited a (Ca2+)i signal necessary for this limiting factor in resynthesis of acetylcholine. 4. The (Ca2+)0 signal necessary for stimulus-induced release of acetylcholine was not affected by HgCl2. Hyperpolarization in K(+)-free solution antagonized the inhibitory effect of HgCl2 at indirect stimulation, and Ca(2+)-free solution enhanced the inhibitory effect at direct stimulation. K+ depolarization, membrane electric field increase with high Ca2+, membrane stabilization with lidocaine, and half-threshold stimulation, did not change the inhibitory effect of HgCl CH3HgCl. 1.85 x 10(-5) M, disclosed a synergistic interaction with caffeine during direct, but not during indirect, stimulation.
Cell Mol Neurobiol 1994 Dec
PMID:Inhibitory effects of HgCl2 on excitation-secretion coupling at the motor nerve terminal and excitation-contraction coupling in the muscle cell. 754 23

This review summarizes the main cellular mechanisms involved in potassium regulation in plasma and skeletal muscle during exercise. The effects of exercise-induced hyperkalemia and post-exercise hypokalemia on the cardiac action potential are reviewed in light of recent research on Na+ and K+ channel activity. Specific consideration is given to K+ release from contracting skeletal muscle, K+ uptake by contracting skeletal muscle, K+ uptake by non-contracting tissues during the period of exercise, and K+ uptake by skeletal muscle recovering from contractile activity. The onset of exercise is associated with a net release of K+ from contracting skeletal muscle that results in an increase in plasma [K+]. Resultant decreases in intracellular [K+] and increases in interstitial [K+] in contracting skeletal muscle have been implicated in the fatigue process. The rate and magnitude of increase in plasma [K+] is dependent on exercise intensity, trained state of the individual, and on drugs such as beta-adrenoceptor blockers and caffeine. During exercise, the uptake of K+ from the blood by non-contracting tissues may be important in preventing plasma [K+] from rising to excessive levels that will impair skeletal muscle and myocardial excitability and contractility. Cessation of exercise results in a rapid decrease in plasma [K+], often to 3 mEq/l or less with intense exercise, that may be maintained for prolonged periods. The rapid increases and decreases in plasma [K+] with onset and cessation of exercise, respectively, has been implicated in altered myocardial function and sudden cardiac death. Recent studies suggest that increases in catecholamines during exercise are cardioprotective to the arrhythmogenic effects of hyperkalemia.
J Mol Cell Cardiol 1995 Apr
PMID:Potassium regulation during exercise and recovery in humans: implications for skeletal and cardiac muscle. 756 98

Potassium release from contracting skeletal muscle cells facilitates ongoing muscle contraction but may also lead to muscular fatigue. This review focuses on the effects of altered physical activity on K+ regulation during exercise, with special emphasis on K+ regulation in humans. Endurance and sprint training specifically enhance prolonged and high intensity exercise performance, respectively. Both forms of training reduce the exercise-induced rise in plasma [K+] at the same absolute exercise work rate and duration and increase the total concentration of Na+,K+ pumps in trained human muscle by approximately 15%. However, the increased pump density has not been proven to account directly for either the reduced hyperkalaemia or the improved exercise performance after training. The most likely factor accounting for the improved K+ regulation after training is an increased activation of Na+,K+ pumps during exercise, but this is not due to increased circulating catecholamine concentrations after training. A chronic reduction in physical activity reduces the muscle Na+K+ pump concentration in animal models, with an augmented exercise-induced rise in plasma [K+]. Thus, physical training enhances, whilst inactivity impairs K+ regulation during exercise, consistent with the improved exercise performance after physical training and the impaired performance with inactivity.
J Mol Cell Cardiol 1995 Apr
PMID:Effects of training on potassium homeostasis during exercise. 756 6

Human skin fibroblasts from young and old donors were cultured in vitro and compared in their mitochondrial morphology and function. A decreased numerical density of mitochondria in the fibroblasts from old individuals was balanced by the increased size of individual mitochondria. The mitochondrial membrane potential, estimated in the intact cells by the difference between the total accumulation ratio of the lipophilic cation tetraphenylphosphonium and the accumulation ratio in presence of uncoupler, was unchanged, as were some mitochondrial enzymatic activities tested in the homogenates. The results point out that the decreased proliferating capacity observed in the fibroblasts from the old subjects was accompanied by a likely decrease of mitochondrial duplication; the decreased energy utilization for cell division balances a possible energetic decline in such way that the steady-state energy status is unchanged.
Biochem Mol Biol Int 1994 Jun
PMID:Lack of major mitochondrial bioenergetic changes in cultured skin fibroblasts from aged individuals. 795 Oct 66

In previous research, rats subjected to prolonged sleep deprivation have shown disturbances of thermoregulation, hormonal and metabolic changes in apparent response to the thermoregulatory problems, lesions on the tail and paws, and eventual death. To search for alterations of functional activity in brain, the expression of the immediate early gene Egr-1 was examined by immunocytochemistry and Northern blotting in rats subjected to total sleep deprivation (TSD) for 10 days. Controls included yoked stimulus-control (TSC) rats, surgically implanted but otherwise undisturbed control rats, and unoperated control rats. Photographs of immunoreacted coronal sections from four sets of rats were ranked blindly for 25 brain regions. TSD rats showed tendencies for regionally specific increases in Egr-1-like immunoreactivity in dorsal raphe, lateral habenula, superior colliculus, and ventral periaqueductal grey. However, most regions showed no differences in Egr-1-like immunoreactivity between TSD and control rats. Neither was there a difference in whole brain Egr-1 mRNA by Northern blot in two additional sets of rats. Thus, this study, like previous studies of brain histology, amines, adrenoceptors, and glucose utilization, does not provide positive support for the hypothesis that sleep protects the central nervous system against massive global damage, fatigue, or dysfunction.
Brain Res Mol Brain Res 1993 Mar
PMID:Expression of Egr-1 in the brain of sleep deprived rats. 851 May 2

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects. Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion. Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects. The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.
Biochem Mol Med 1996 Apr
PMID:Preliminary determination of a molecular basis of chronic fatigue syndrome. 873 84

In rats with left ventricular (LV) hypertrophy, we investigated whether abnormalities of skeletal muscle could result in reduced exercise tolerance in the absence of reduced cardiac function. LV pressure overload was induced by partial constriction of the abdominal aorta (AC) with controls subjected to sham operation. Cardiac and skeletal muscle function and blood flow were assessed in vivo 3 and 6 weeks later. AC induced LV hypertrophy of 41% and 37% at 3 and 6 weeks post-operation. In AC rats, cardiac index was 31 +/- 8 and 35 +/- 4 ml/min/100 g at 3 and 6 weeks compared to 38 +/- 4 and 34 +/- 2 ml/min/100 g in controls (N.S.). Fatigue index of the soleus (type-I rich) muscle in AC rats was reduced by 14% (P < 0.05) at both time points, while that of the tibialis anterior (mixed fiber) muscle was unchanged at 3 weeks but reduced by 18% (P < 0.05) at 6 weeks. Function of the extensor digitorum longus (type-IIB rich) muscle was unaltered at both time points. Blood flow at rest was paradoxically increased in muscles which exhibited increased fatigue susceptibility. At 3 weeks, blood flow during fatigue stimulation was reduced by 33% in the soleus muscle; the only muscle to exhibit impaired fatigue resistance at this time point. Blood flow during stimulation remained unaltered in the EDL and TA muscles. Thus, impaired fatigue resistance was observed in skeletal muscle with high oxidative and oxidative glycolytic fiber content during the compensatory phase of LV hypertrophy, prior to overt cardiac dysfunction. A selective impairment of blood flow to these muscles during exercise may play a causal role in exercise intolerance.
J Mol Cell Cardiol 1996 Jan
PMID:Impaired skeletal muscle fatigue resistance in rats with pressure overload-induced left ventricular hypertrophy. 874 26

The potential relationships between chlorinated hydrocarbon contamination in human serum and red/white blood cell profiles were investigated by multivariate techniques to assess the cellular response patterns to high and low organochlorine levels in the serum. Twenty-three healthy control subjects and fourteen patients with unexplained and persistent fatigue were divided on the basis of (a) high or low total organochlorine content, (b) high or low DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethene) content, and (c) high or low HCB (hexachlorobenzene) content. Discriminant function analysis revealed that the groups with high organochlorine content had significantly different red/white blood cell profiles compared with the low organochlorine groups ((a) P < 0.017, (b) P < 0.015, and (c) P < 0.0002). As a variable, the percentage of neutrophils was the most important discriminant parameter for differentiating between the high and low total organochlorine groups. Thirteen of the fourteen fatigued patients were characterized as "high total organocholorine content" (P < 0.04). The red cell distribution width was elevated in the high DDE group (P < 0.04) and was the most important discriminant parameter for differentiating between the high and low DDE groups. The percentage of eosinophils and the hemoglobin content were both reduced in the high HCB group (P < 0.009,P < 0.003, respectively) and the percentage of eosinophils was the most important discriminant parameter for differentiating between the high and low HCB groups. Those patients with unexplained and persistent fatigue had significantly higher levels of DDE compared with the controls and had different specific blood cell responses to organochlorines compared with control subjects.
Biochem Mol Med 1996 Jun
PMID:Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters. 880 49

Chronic fatigue syndrome (CFS) patients have a urinary metabolite labeled CFSUM1 with increased incidence (P < 0.004) and relative abundance (P < 0.00003). The relative abundances of urinary CFSUM1 and beta-alanine were associated with alterations in metabolite excretion and symptom incidence. In 20 CFS patients and 45 non-CFS subjects, symptom/metabolite associations were investigated by assessing symptom sensitivity and specificity, and symptom indices of total symptom incidence, CFS core symptoms, cognitive, neurological, musculoskeletal, gastrointestinal, infection-related and genitourinary symptom indices, as well as a visual analogue pain scale of average pain intensity. Thirty-three symptoms had significant (P < 0.005) sensitivity and specificity in the CFS patients compared to that in the non-CFS controls. Severe fatigue was the only symptom with 100% sensitivity and specificity and CFSUM1 excretion was the primary metabolite for expression of this symptom. All nine symptom indices had elevated responses in the CFS patients (all P < 0.0000001). Multiple regression analyses indicated that all the symptom indices had significant correlations (R) with changes in the urinary excretion of metabolites (P < 0.0001). CFSUM1 and beta-alanine were the first and second metabolites correlated with the CFS core symptom index and CFSUM1 was primarily associated with infection-related and musculoskeletal indices whereas beta-alanine was primarily associated with gastrointestinal and genitourinary indices. The strong associations of CFSUM1 and beta-alanine with CFS symptom expression provide a molecular basis for developing an objective test for CFS.
Biochem Mol Med 1996 Jun
PMID:Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome. 880 50

Congestive heart failure is often associated with skeletal muscle abnormalities that contribute to early fatigue and acidosis. Up to the present time, however, the mechanisms responsible for these changes are unclear. Myocardial infarctions were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10 control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1 +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)] underwent in vivo measurements of total body, and soleus total protein and myosin heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was also analysed for protein content, and MHC isoenzyme content by SDS-PAGE. Northern blotting also was used to determine levels of the mRNA's encoding type I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5 mg) and the degree of atrophy was significant when corrected for body mass (0.38 +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant difference in plasma leucine flux (an index of whole-body protein synthesis), soleus muscle total and MHC synthesis was reduced in heart failure animals. Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding beta MHC were significantly depressed in the heart failure rats, where those encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha-skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH) were also significantly depressed. This animal model of chronic heart failure is associated with quantitative and qualitative alterations in skeletal muscle gene expression that are similar to those reported in skeletal muscle of patients with chronic heart failure. The altered phenotype and impaired metabolic capacity may contribute to exercise intolerance in CHF.
J Mol Cell Cardiol 1996 Aug
PMID:Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure. 887 78


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