Biomedical subjects

R Rüdel

Publications and source records attributed to R Rüdel.

At least 91 records · Page 5Linked to original sources

PubMed1989

Abnormalities of the fast sodium current in myotonic dystrophy, recessive generalized myotonia, and adynamia episodica.

Myoballs, i.e., spherical muscle cell regenerates, were cultured from the biopsied muscles of three patients with myotonic dystrophy, three patients with recessive generalized myotonia, and a patient with adynamia episodica. The membrane of these myoballs was voltage-clamped in the whole-cell mode for the recording of sodium currents (at 11, 24, and 37 degrees C). The voltage dependence of the steady-state activation and inactivation curves showed only minor abnormalities in all cases. The time constants of activation (tau m) and inactivation (tau h), when studied at the three temperatures, showed a characteristic pattern of abnormalities. In myotonic dystrophy, both tau m and tau h were larger than control; in recessive generalized myotonia and adynamia episodica both tau m and tau h were smaller than control. In the latter diseases, these time constants also showed a smaller than normal decrease with membrane depolarization. The changes seen for recessive generalized myotonia and adynamia episodica would favour the occurrence of myotonia, the opposite results for myotonic dystrophy would oppose myotonia.

Action Potentials↗

PubMed1989

Thyrotoxic periodic paralysis and the sodium/potassium pump.

The hypothesis of altered Na+/K+ transport in thyrotoxic periodic paralysis (TPP) was tested in an investigation of the K+ influx into erythrocytes from two patients with episodes of thyrotoxic muscle weakness. A patient with primary hypokalemic periodic paralysis (HPP) and three healthy volunteers served as controls. The TPP patients were of Oriental and Caucasian origin and differed in their clinical symptoms. For the Caucasian patient, the Na+ content of the erythrocytes was twice the control, for the Oriental patient it was normal. The K+ dependence of the ouabain-inhibitable K+ influx (the pump action) was also abnormal in the Caucasian patient, the flux being 70% of control at 2 mM [K+]e and normal at 4 mM [K+]e. The K+ influx was normal in the Oriental patient. By contrast, the K+ leak of the cells was normal in the Caucasian and was increased in the Oriental patient. The pump/leak ratio was thus reduced in both TPP patients. All parameters investigated were normal in the patient with primary HPP. It is concluded that the ion transport systems of muscle may be altered in TPP, but that the patho-mechanism might be different in the rare Caucasian cases and the rather more common Oriental cases.

Adolescent↗

PubMed1989

Adynamia episodica hereditaria: what causes the weakness?

The cause of weakness was investigated in a patient with adynamia episodica hereditaria without myotonia. A pattern of exercise and rest produced episodes of hyperkalemic periodic paralysis. In addition, local muscle weakness was induced by forearm cooling. Investigations on isolated intercostal muscle demonstrated that a high potassium concentration in the bathing solution triggered a noninactivating membrane current causing depolarization of the muscle fibers. This current was carried by sodium as it could be inhibited by tetrodotoxin. The abnormal sodium conductance led to an increase of sodium within the fibers. This was demonstrated directly by intracellular recordings. Weakness induced by rest after exercise and cold-induced weakness appeared to have different pathomechanisms. In the cold, the muscle fibers retained a normal resting potential, but their excitability was reduced and their mechanical threshold was increased. These findings also provide evidence that the mechanism of cold-induced weakness in adynamia episodica is distinctly different from the cold-induced weakness that occurs in paramyotonia congenita.

Adult↗

PubMed1989

Ultrastructure of the contractile apparatus of rat skeletal muscle embedded in an aqueous medium.

The method of tissue embedding in melamine resin was applied to rat skeletal muscle. This method does not require tissue dehydration with organic solvents; only aqueous solutions are used. Electron micrographs of muscles embedded in melamine differ from those embedded in the conventional epoxy resin. In melamine-embedded muscles the actin and myosin filaments appear larger in diameter and subunits can be recognized in cross-sectioned myosin filaments. Within the Z-line, the characteristic patterns described for muscles embedded in epoxy resin are not visible; the spaces between the actin filaments are filled with electron-dense material. This suggests that the Z-line is more compact than could be concluded from epoxy resin-embedded muscle specimens. The M-line appears to be different from what is observed in epoxy-embedded muscle. The membranes appear as several clearly delineated layers. Dehydration rather than the action of the organic solvents per se is the main reason for the differences in the structure of the contractile apparatus between melamine- and epoxy-embedded muscles.

Actin Cytoskeleton↗

PubMed1988

The effects of space charge on the ionic currents through biological membranes.

In this paper, the ions moving through an ion-selective membrane are regarded as a space charge. The repulsive action among the ions attenuates the ion current through the membrane. For a quantitative description of this effect on the relation between the ion current, the ion concentrations and the membrane voltage, the usual assumption of a constant electric field within the membrane is replaced by that of an inconstant field influenced by the moving ions. This can be done either by inserting the Poisson equation into the Nernst-Planck equation or by directly calculating the Coulomb forces, e.g. between two ions moving through a narrow channel. An attenuation factor is defined and its dependence on membrane thickness, dielectric number, membrane voltage, and ion concentrations is exactly calculated; its dependence on the cross section of an assumed channel is necessary for the current through the channel to be appreciably attenuated by saturation effects. The saturation effect described differs from the Michaelis-Menten kinetics in that no absolute maximum effect is attained.

Cell Membrane Permeability↗

PubMed1988

Transient weakness and altered membrane characteristic in recessive generalized myotonia (Becker).

The isometric force of arm and leg muscles was studied in five unrelated patients with recessive generalized myotonia (Becker). The symptom of myotonia was present mainly in the legs, whereas transient weakness was the prominent symptom in the arms. Tocainide improved both symptoms, although it improved the stiffness more than the weakness. A specimen of intact muscle fibers was excised from the external intercostal muscle of one of the patients. The resting potential of the fibers was normal, but on injection of depolarizing current the fibers responded with repetitive action potentials. In normal interstitial fluid the current-voltage relationship was N-shaped, with a region of negative slope between -70 and -55 mV. Replacement of chloride by an impermeant anion changed this relationship very little, suggesting an abnormally small chloride conductance. The potassium current through the inward-going rectifier was larger than normal. The force of tetanic contractions of a rested bundle was not sustained but fell quickly to a plateau that increased with repeated stimulation. The relaxation of a rested tetanus was slow and accompanied by spontaneous electrical activity. In subsequent contractions the relaxation became faster and electrical after-activity decreased. However at 23 degrees C the speed of relaxation was always high despite a large amount of electrical after-activity. The electrical instability of the membrane and the transient weakness can be explained on the basis of the N-shaped membrane characteristic.

Action Potentials↗

PubMed1988

The membrane lipid and fatty acid composition of erythrocyte ghosts from three patients with paramyotonia congenita.

The membrane lipid and fatty acid composition of red blood cell ghosts from three paramyotonia patients was investigated. Cholesterol and total phospholipid contents were not different from the controls, but the sphingomyelin content was reduced, and this was compensated for by an increase in phosphatidylcholine. Thus, the molar ratios of phosphatidylcholine/sphingomyelin and phophatidylcholine/phosphatidylethanolamine were greater than normal. The saturated fatty acids in the total phospholipids were increased so that the ratio of saturated/unsaturated fatty acids was 1.4-1.6 versus 1.1-1.2 in the controls. The polyunsaturated fatty acids comprised only 22-26% of the fatty acids versus 31-32% in controls. The reduction in content of unsaturated fatty acids concerned all phospholipid classes in one patient and only the choline phospholipids in the tow other patients who were related to each other. The pattern of the fatty acids in the C2-position of the glycerophospholipids reflected the finding in the total phospholipids. Thus, an alteration of the activity of the acyl-CoA: 1-mono-acylphosphoglyceride-acyltransferase seems unlikely. The results support the notion of a generalized membrane defect in paramyotonia congenita, although the degree of abnormality in the fatty acid pattern was not correlated with the severity of the clinical symptoms.

Adult↗

PubMed1988

Drug-induced myotonia in human intercostal muscle.

The myotonia-inducing effects of furosemide and clofibrate, two widely used pharmaceutical agents, were investigated in excised human external intercostal muscle. The effects of anthracene-9-carboxylic acid (9-AC), a well-known myotonia-producing chemical, were also tested for comparison. In the presence of these drugs the electrical threshold was lowered, and a constant current pulse produced multiple spiking. Short trains of direct stimuli were often followed by after-activity, and this caused a myotonia-like prolongation of muscle contraction. Voltage-clamp experiments showed that 0.05 mM anthracene-9-carboxylic acid, 1 mM furosemide, and 1 mM clofibrate decreased the chloride conductance of the muscle fiber membrane to 14, 18, and 40%, respectively, of the normal value, and the myotonia-inducing potency of the 3 drugs was correlated with the decreased chloride conductance. The potassium currents were not affected by these compounds.

Anthracenes↗

PubMed1988

Hodgkin-Huxley parameters of the sodium channels in human myoballs.

Myoballs were cultured from biopsies of adult human skeletal muscle without the use of antimitotic drugs. The sodium currents flowing during stepwise depolarization of the myoball membrane were investigated with the wholecell recording technique. The temperature range covered 10-37 degrees C. Two types of sodium channel were distinguished by their different sensitivity to tetrodotoxin (TTX). The channel with normal TTX sensitivity seemed identical with the sodium channel in adult muscle, the channel with less TTX sensitivity seemed identical with the juvenile channel found in developing and in denervated muscle. The activation and inactivation parameters of both channel types were quantitatively determined. The activation parameters of the two channel types were identical, but in comparison to the h infinity-curve of the adult sodium channels the h infinity-curve of the juvenile channels was positioned at more negative potentials, had a less steep slope, and when the temperature was decreased, its point of inflection shifted more in negative direction.

Aged↗

PubMed1988

Differential effects of halothane on adult and juvenile sodium channels in human muscle.

Myoballs were cultured from biopsies of adult human skeletal muscle. Transient currents through the sodium channels were elicited by depolarizing a myoball membrane with the whole-cell patch-clamp technique. The properties of the sodium channels were determined from the Hodgkin-Huxley parameters (INa max, tau m, tau h, h infinity-curve) derived from these transients. Halothane, when applied at 3.4 mmol/l (approximately 15 kPa), blocked about 50% of the current through the adult, TTX-sensitive sodium channels but had little effect on the current through the juvenile, TTX-insensitive sodium channels. At greater than 12 mmol/l, halothane blocked both channel types completely. The time constants of activation and inactivation were decreased in the presence of 3.4 mmol/l halothane but not enough to account for the decrease of the current amplitude. Halothane shifted the h infinity-curves of both channel types toward more negative potentials by an amount that was roughly proportional to its concentration. Myoballs from a man susceptible to malignant hyperthermia (MH) gave the same results as the controls indicating that the halothane effect on the action potential of MH-susceptible muscle are not mediated by a specific effect on the sodium channels.

Action Potentials↗

PubMed1987

Inactivation of TTX-sensitive and TTX-insensitive sodium channels of rat myoballs.

Myoballs, spherical muscle cell regenerates, have two types of Na+ channels, the adult type with a high sensitivity to the Na+ channel blocker tetrodotoxin (TTX), and the juvenile type with 10 times less TTX sensitivity. The potential dependence of the steady-state inactivation of the Na+ channels (h infinity-curve) was studied in 50 rat myoballs with the whole-cell patch-clamp method which provides overall results from all the Na+ channels in an investigated myoball. At 37 degrees C, the h infinity-curve had the usual shape, but below 30 degrees C it was indented in a way suggesting contributions from two populations of Na+ channels with a different potential dependence of inactivation. A more distinct separation of the two components was possible by differentiating the h infinity-curve with respect to the prepulse potential. The population requiring a more negative potential for the removal of inactivation had a low sensitivity to TTX while the other population had TTX sensitivity similar to that of Na+ channels in adult muscle. At 37 degrees C, the separation between the two h infinity-curves was small. At lower temperatures, the separation became larger. This change was almost entirely due to the h infinity-curve of the TTX-insensitive channels shifting towards more negative membrane potentials.

Age Factors↗

PubMed1987

Adynamia episodica hereditaria with myotonia: a non-inactivating sodium current and the effect of extracellular pH.

To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K]e, was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than -80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to -63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to -57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K]e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l.

Adult↗

PubMed1987

Membrane defects in paramyotonia congenita (Eulenburg).

Membrane potentials, current-voltage relationships, and component conductances were determined in resting excised external intercostal muscle fibers from five patients with paramyotonia congenita. At 37 degrees C all investigated parameters were normal. At 27 degrees C the resting potentials decreased to about -40 mV, and the fibers were inexcitable. At this stage the membrane currents were much larger than in normal fibers owing to increases in the membrane conductances for Na and Cl ions. The earlier finding that in the cold the Na permeability is abnormally large was confirmed. The Cl permeability was shown to be normal even in the cold. The decrease of the resting potential and the changes in the current-voltage relationship at 27 degrees C could be prevented by the use of the Na channel blocker tetrodotoxin (TTX) or by bathing the fibers in a Na-free solution. Our previous conclusion that the Cl conductance at 27 degrees C was also increased when TTX was present was not confirmed. Exposure of a muscle bundle to 7 mmol/l potassium did not lead to excessive depolarization and paralysis.

Biopsy↗

PubMed1987

Cultivation, morphology, and electrophysiology of contractile rat myoballs.

Myoballs were cultured from neonatal rat skeletal muscle without the use of antimitotic drugs. Electron microscopic investigation showed that 7-day-old myoballs are multinucleated syncytia in a state of differentiation where filaments are abundant and already in hexagonal arrays. The resting potential of 142 myoballs kept at 20 degrees C was not correlated with the cell size. Its mean value was -64 mV. Cells with a high resting potential were capable of generating action potentials with a threshold of -51 mV, an overshoot of +31 mV, and a rate of rise of 100 V/s. The steady-state current-voltage relation showed inward rectification on hyperpolarization and outward rectification on depolarization. The dynamic sodium and potassium currents were investigated at 37 degrees C with the whole-cell-recording technique. The sodium current had its maximum at -20 mV. The potassium current showed delayed activation and a very slow and incomplete inactivation. The electrophysiological results from these cultured cells are very similar to those obtained from adult cells.

Action Potentials↗

PubMed1987

Dependence of the electrogenic pump current of Xenopus oocytes on external potassium.

The membrane potential of Xenopus oocytes showed a variable response to an increase of the K+ concentration in the bathing solution, [K+]e, from 2.5 mM to 20 mM. In 54% of the cases (n = 52) the cells hyperpolarized (by max. 70 mV). In the presence of 10(-5) M ouabain, all cells depolarized suggesting that the hyperpolarization was caused by an electrogenic Na+/K+ pump. In cells stored overnight in a Na+-free solution the transition from 2.5 to 20 mM [K+]e always caused depolarization indicating that the stimulation of the pump requires high internal sodium, [Na+]i. Cells stored overnight in a Na+-rich solution had a [Na+]i of 30.7 +/- 7 mM, i.e. the Na+/K+ pump was saturated with sodium (Lafaire and Schwarz 1986). With 9 such cells we determined the K+ activation of the Na+/K+ pump. The activation follows Hill kinetics with Imax = 90.5 nA, Ks = 2.3 mM, and n = 1.68.

Animals↗

PubMed1987

Ion transport systems in erythrocytes from paramyotonia patients.

To test the hypothesis of a general defect in the ion transport systems in the cell membranes of patients with paramyotonia congenita, we measured the ouabain-inhibitable and the furosemide-inhibitable K+ influxes in erythrocytes from two patients. In the temperature range examined (15-40 degrees C), the ouabain-inhibitable flux did not differ significantly from control. Also the furosemide-inhibitable flux was well in the rather large control range. The dependence of these fluxes on the external K+ concentration was normal. Energy depletion of the erythrocytes by preincubation with desoxy-glucose led to reduced K+ influxes that were not significantly different in patients and controls. The results do not support the hypothesis of a general defect in the ion transport systems in paramyotonia; they do, however, not rule out the possibility that the ion transport systems in paramyotonic skeletal muscle are defect.

Adult↗

PubMed1986

Muscle stiffness and electrical activity in paramyotonia congenita.

To investigate the pathomechanism of paramyotonic stiffness, the mechanogram of isometric finger force and the electromyogram of the flexor digitorum muscle were simultaneously recorded in five unrelated paramyotonia congenita patients. Cooling of the forearm provoked "spontaneous" electrical activity, but the accompanying force was less than 5% of the maximal voluntary isometric contraction amplitude. The relaxation of maximal voluntary contractions executed in the cold had a normal first phase and a very slow second phase. The force amplitude at the beginning of the slow phase was up to 80% of the maximal contraction amplitude; the duration of the slow phase was up to several minutes. It was concluded that the slowed muscle relaxation is more important as a factor contributing to paramyotonic stiffness than spontaneous force generation. Involuntary electrical activity recorded during the slow relaxation phase was too low to account for the force. Intercostal muscle biopsies obtained from four patients showed similar phases of slow relaxation when stimulated to give isometric twitches or tetani in the cold. Extracellular recording with electrodes designed to pick up all activity from the small bundles clearly showed that the slow relaxation phase was not caused by spontaneous action potentials. One possible explanation for the slowed relaxation is a long-lasting depolarization-induced contracture of the muscle fibers following activation in the cold.

Adult↗

PubMed1986

Correlation between the light diffraction pattern and the structure of a muscle fibre realized with Ewald's construction.

Ewald's construction of reciprocal space is used to explain the diffraction pattern obtained by illumination of a skeletal muscle fibre with laser light. The question of whether the illuminated fibre segment acts as a monocrystal or as a conglomerate of crystallites is answered by determining the longitudinal extension of the layer lines; neither the whole muscle fibre nor the single myofibril acts as the diffracting unit. The characteristic fine structure within a layer line ('streaks') is explained by Ewald's formalism as being caused by diffraction from partial volumes of the illuminated fibre segment. These partial volumes constitute the main diffracting units. Any cross-section of a 100 micron diameter fibre contains 3-6 such units. They are delineated from each other by the skew of the diffracting planes with respect to the fibre axis, and possibly by small differences in sarcomere length. Within a unit, skew angle and sarcomere length are nearly constant. Light intensity measurements along the length of a layer line at various tilt angles (omega) between fibre and beam axis provide an overview of the size and the skew angle of the various diffracting units within the illuminated fibre segment. The cross-sections of the diffracting units were measured in 'mini'-omega-scans of streaks created by them and from the maximal streak length. In general, the units had noncircular cross-section, the length of the main axis ranging between 10 micron and the fibre diameter. The axial extensions of the diffracting units determined in fibre length scans was 100-300 micron. The results of diffraction experiments reported in the literature as well as the data from light and electron microscopy are in agreement with the fibre structure suggested above. Sarcomere length determination by light diffractometry is discussed within the framework of the Ewald formalism, and recommendations for an experimental procedure are given.

Animals↗