Comparative effects of ischemia and acute hypoxemia on muscle afferents from tibialis anterior in cats

Comparative effects of ischemia and acute hypoxemia (PaO₂ = 24 mm Hg) were studied in anesthetized cats on afferents from the tibialis anterior limb muscle. Metaboreceptors (groups III and IV fibers) and mechanoreceptors were identified by their activation by an intraarterial injection of lactic acid (LA) or high-frequency vibrations (HFV) applied to the extremity of the muscle tendon, respectively. Ischemia and hypoxemia exerted opposite influences on the two categories of muscle afferents: they depressed the response of mechanoreceptors to HFV, but markedly enhanced the spontaneous tonic activity of metaboreceptors. The effects of hypoxamia were delayed but slightly greater and lasted longer during the recovery period than those exerted by ischemia. The inhibitory action on mechanoreceptors exerted by a reduced oxyden supply to muscle is interpreted as a result from local acidosis. Indeed, under normoxic conditions, a LA bolus injection during the HFV test also reduced the firing rate of these receptors. © 1993 John Wiley & Sons, Inc.     

Is monoamine oxidase inhibitor induced myoclonus serotoninergically mediated?

Summary In the present study a single case observation of myoclonus during sleep-wave transition was monitored in a depressed patient treated with the monoamine oxidase inhibitor, phenelzine. The myoclonus had a rhythm of 1 c/second and lasted for two years, the duration of phenelzine treatment. Myoclonus appeared neither during wakefulness nor during sleep, but at wake-sleep-wake transitions. This switch myoclonus was associated with phasic muscle hyperactivity during REM sleep.Methysergide a 5-HT suppressor, decreased the switch myoclonus frequency and the REM muscle hyperactivity, indicating serotoninergic involvement in the mechanism of phenelzine induced myoclonus.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Phorbol ester does not mimic,but antagonizes the alpha-adrenoceptor-mediated positive inotropic effect in the rabbit papillary muscle

Summary The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) was used to examine the hypothesis that phosphoinositide turnover is involved in the regulation of myocardial contractility mediated by stimulation of alpha-adrenoceptors in the mammalian cardiac muscle. Exposure of the isolated rabbit papillary muscle electrically driven at a rate of 1 Hz at a temperature of 37°C to TPA in concentrations of 10–1000 nmol/l for 30 min did not affect the basal force of contraction. The concentration-response curve for the positive inotropic effect of (–)-phenylephrine mediated by stimulation of alpha-adrenoceptors in the presence of (±)-bupranolol (100 nmol/1) was shifted to the right and downward by TPA in concentrations of 30–1000 nmol/l, while the effect of (–)-phenylephrine mediated by stimulation of beta-adrenoceptors in the presence of prazosin (100 nmol/l) was not decreased, but slightly enhanced by exposure of the muscle to relatively low concentrations of TPA (10–100 nmol/l). Incubation of the membrane fraction isolated from the rabbit ventricular muscle with TPA in vitro under the same condition as employed in the physiological experiments decreased the specific binding of [³H]prazosin but not that of [³H]CGP-12177, while the non-tumor promoting phorbol ester, PDD, was ineffective. These results indicate that activation of protein kinase C by TPA does not mimic the positive inotropic effect of catecholamines mediated by activation of myocardial alpha-adrenoceptors. on the other hand, the specific interaction of alpha-adrenoceptor-mediated processes with TPA in the rabbit papillary muscle is in line with the view that the facilitation of phosphoinositide turnover and subsequent activation of protein kinase C may play a certain role in the coupling of alpha-adrenoceptor occupation by agonists to the process leading to the positive inotropic action. Send offprint requests to M. Endoh     

The depressing effect of tetracaine and ryanodine on the slow outward current correlated with that of contraction in voltage-clamped frog muscle fibres

The effects of tetracaine (10–50 M) and ryanodine (0.1–10 M) were tested on the slow outward K⁺ current (I _so) and the mechanical tension of isolated frog muscle fibres in a voltage-clamp device (double mannitol-gap) connected to a mechanoelectric transducer. In the concentration range tested, both drugs induced a simultaneous inhibition of tension and current. In all cases the effect on tension was twice that on current. The tetracaine-induced current and tension blocks were fully reversible and dose-dependent. In contrast the ryanodine effects on current and tension were not reversible and did not exhibit a dose dependence except for the delay before the onset of the response, which was shortened when the concentration was raised. Linear regression analysis of the time-dependent and dose-dependent effects of both drugs indicated a strong correlation between the decreases in tension and current. It is concluded that the slow outward current is partly under the control of the Ca²⁺ release from sarcoplasmic reticulum during contraction.     

Plateau potentials evoked by climbing-fibre stimulation are restricted to the Purkinje cell dendrites of the cat

The present study investigated the duration of afterdepolarizations in Purkinje cell somata following climbing-fibre activation. Intracellular recordings revealed that, in cells with membrane potentials more negative than -50 mV and with normal spike-generating capabilities, climbing-fibre activation resulted in somatic responses with short afterdepolarizations. As the cell deteriorated and the resting membrane potential became more positive, the duration and form of the climbing-fibre response resembled the plateau potentials recorded from proximal dendrites. The absence of plateau potentials in undamaged Purkinje cell somata was confirmed by extracellular recording of test spike amplitudes following evoked climbing-fibre responses.     

Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques

Summary Different regions of human aorta and of other human arteries obtained at autopsy were analyzed with regard to their topography and to the different stages of arteriosclerosis. Material was studied by immunocytochemical techniques with antibodies specific for either desmin (D) or for vimentin (V), the two types of intermediate filament proteins present in vascular smooth muscle cells. In normal arteries endothelial cells as well as the adjacent intimal cells were D–V+. In the media D+V+ as well as D–V+ cells were present, with the relative numbers of each cell type dependent on the particular blood vessel. When cells in arteriosclerotic plaques at different stages of development were examined an occasional plaque showed cells of the D+V+ type. In the majority of plaques however the cells were V– D+. In plaques where severe ulceration and necrotic material was present D–V+ cells were found at the border of the lesion: foam cells when they could be identified appeared to be D–V+.     

Intramuscular pressure,EMG and blood flow during low-level prolonged static contraction in man

Seven men performed one-legged isometric knee-extension at 5% MVC for 1 h. Intramuscular pressure increased with contraction from its resting value of 14 (2–31) mmHg. Some intramuscular pressure recordings stayed at an almost constant level throught the 1 h contraction, but most recordings showed large fluctuations from resting values up to 90 mmHg. The overall mean intramuscular pressure was twice the resting value. In some cases, EMG recordings confirmed that the changes in intramuscular pressure were related to alternating recruitment of various parts of the knee-extensors. Blood flow in the femoral vein increased within 3 min of 5% MVC to a level of 1.58 (1.25-2.22) 1 min^-1 and no significant changes occurred during the 1 h contraction. In two subjects blood flow was measured also in the recovery period, and this decreased almost immediately when the muscle relaxed. It is concluded that during low-level static contractions, the blood supply to the exercising muscle is maintained at a sufficiently high level, and that the alternating recruitment of muscle fibres may result in a heterogeneously distributed blood flow within the contracting muscle. Despite this the muscle was fatigued after the 1 h at 5 % MVC. The rating of perceived exertion (RPE) increased from 1.9 (1–3) at the beginning to 4.5(2–8) at the end of contraction, and MVC was decreased by 12% after the contraction.     

Calcium transport and ATPase activity in mitochondria and fragments of sarcoplasmic reticulum of the heart and muscles of rabbits with hypercholesteremia

Keeping rabbits on a high-cholesterol diet (1 g/kg) for 3–7 months led to an increase in cholesterol concentration in the mitochondrial membranes and fragments of the sarcoplasmic reticulum (SPR) of the myocardium and skeletal muscles. Saturation of the membranes with cholesterol led to a decrease in efficiency of the Ca-pump of the SPR, as reflected in lowering of the Ca/ATP ratio and an increase in the outflow of Ca⁺⁺ from the SPR. Under these conditions the rate of accumulation of Ca⁺⁺ was higher in SPR than in the mitochondria. Activity of mitochondrial Mg⁺⁺-activated 2,4-DNP-ATPase was reduced in hypercholesteremia.Laboratory of Molecular Pathology and Biochemistry, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 292–294, March, 1980.     

Spectral analysis of spontaneous contractions of the isolated portal vein of rats

Summary The spontaneous contractions of segments of rat portal veins have been examined in vitro under isotonic and isometric conditions. The power density spectra of recorded time series lasting 10–60 min were calculated. The spectra usually consist of harmonic frequency components. Only during shorter periods of analysis (10 min time series) we sometimes found additional non-harmonic components. All frequency components are proportionally shifted by changes of the bath temperature according to an average Q₁₀ of 2.0. Increase of the load decreases the frequency of the contractions.The results of the spectral analysis, indicating a preponderance of a single source of periodicity, were supported by direct evidence of a pacemaker region. By recording contractions after systematic dissections of the portal vein segment, we found that spontaneous activity is generated at the central end of the segment.This work was supported by the Austrian Research Fund