Veratridine-induced high-frequency asynchronous release of inhibitory transmitter quanta in crayfish nerve-muscle synapses superfused with normal and low-calcium saline

Crayfish fibres of opener muscles were voltage clamped toE=–80 mV membrane potential (T=19–22°C), and veratridine (10–100 mol/l) was added to the superfusate. Within 30–60 s this caused large fluctuations of the clamp current due to vigorous asynchronous quantal release from the inhibitory nerve terminals along the muscle fibre. Excitatory postsynaptic receptors were previously desensitized by application of 5 mmol/l glutamate. Current fluctuations were evaluated by means of the noise analysis technique. Typically, 100 mol/l veratridine increased instantaneously the quantal release rate ñ from ñ<1 quantum/s toñ10,000 quanta/s. Thereafter, ñ declined exponentially with a time constant of 70s. On average, about 500,000 inhibitory quanta could be liberated in this way from the terminals on a single muscle fibre of 1 mm length. Serotonin (1 mol/l) facilitated the effect of lower veratridine concentrations (1–10 mol/l). In opener muscles veratridine-induced asynchronous quantal release showed little dependence on the bath concentration of Ca²⁺. The opposite was found for fibres of the superficial abdominal extensor muscle. Beside postsynaptic current fluctuations, veratridine elicited slowly changing average postsynaptic DC-currents which could be explained partly by superposition of individual inhibitory quantal currents. These DC-currents suggest that beside inhibitory quantal release another factor activates inhibitory postsynaptic receptors after application of veratridine.This investigation was supported by the Deutsche Forschungsgemeinschaft, SFB 220     

Interferon-γ-like immunoreactivity in developing rat spinal ganglia neuronsin vivo andin vitro

Summary Interferon--like immunoreactivity was observed in a subpopulation of 16-day-old embryonic rat spinal ganglion neurons using two monoclonal antibodies directed against different epitopes of recombinant interferon-. During ontogenesis bothin vivo andin vitro, it was found that the strong immunoreactivity was confined to small neurons when neurons become morphologically distinct on the basis of size.In vivo, the interferon--immunoreactive neurons started to express major histocompatibility complex class I antigens after the first postnatal week, whilein vitro no such antigen could be detected. A quantitative Elisa method was developed to determine the levels of major histocompatibility complex class I and interferon-in vitro, whereby increased amounts of major histocompatibility complex class I antigen was detected after exposing the cultures to recombinant interferon- and Sendai virus. Sendai virus also caused a small increase in interferon- with a peak about 12 hours after infection. Thein vitro system will be used to study further the role of the putative neuronal interferon--like molecule in the regulation of cell growth, for induction of major histocompatibility complex antigens and in virus infection of sensory neurons.     

Isoenzymes of γ-glutamyl transpeptidase in liver diseases

Summary A new method for the separation of isoenzymes of-glutamyl-transpeptidase is described, using electrophoresis on acetate cellulose gel and a developing solution composed by-glutamyl-naphthylamide, and a colored diazonium compound.The method permits the separation of up to four different isoenzymes, which we called-GT₁,-GT₂,-GT₃,-GT₄, the first two showing an electrophoretic migration similar to that of ₁- and ₂-globulins and the other two to that of-globulins.The present technique has proved its usefulness in detecting isoenzymes in serum with values of total-glutamyl-transpeptidase higher than 80 U/L.The application of this method in 52 patients with different types of biliary obstruction and hepatocellular damage has shown that it provides new possibilities in differential diagnosis.     

An hypothesis regarding the cortical mechanisms of operative memory

Investigations of the neuronal activity of the cerebral cortex of monkeys during the performance of a delayed spatial choice made it possible to formulate an hypothesis regarding the neuronal systems providing for operative memory. One system functions on the principle of relay race-reverberation transmission of information. During the action of a sensory signal a population of spatially selective sensory neurons is excited. By the delay period (operative memory) this information is transmitted to a population of memory neurons. The delay period is quantized in time segments in the course of which individual populations of cells are involved in relays in the reverberation activity. Each of these populations comprises a neuronal trap in which the excitation circulates for 1.5–2 sec. At the end of the delay period switching of the excitation to a different population of cells takes place, which are associated with the preparation of a goal-directed movement (the neurons of the motor programs). Another system of neurons assures the reliability of the transitional phases of the above-named processes, specifically: 1) of the switchings of information from the sensory neurons to the memory neurons and subsequently to the neurons of the motor programs; 2) the reflection of the entire period of operative memory without relay race-reverberation; and 3) the preservation of the signal information in the activity of a unified neuronal population right up to the moment of the performance of the goal-directed movement. The above-designated systems are represented variously in the associative (frontal and parietal) zones of the neocortex.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 41, No. 6, pp. 1088–1093, November–December, 1991.     

Die Nebennierenrindenfunktion unter Applikation von 9α-Fluorcortisol

Zusammenfassung Untersuchungen über den Einfluß von 9-Fluorcortisol auf die Nebennierenrindenfunktion ergaben — in Verbindung mit in der Literatur mitgeteilten Werten — eine dosisabhängige Einschränkung der Ausscheidung von Nebennierenrindenhormonen. Die Ansprechbarkeit der Nebennierenrinde auf exogenes ACTH bleibt erhalten. Es ist daher eine Hemmung der hypophysären ACTH-Sekretion anzunehmen, die durch die Struktur des synthetischen Steroids erklärbar ist. — In geringer Dosierung, wie sie als Erhaltungsdosis bei Langzeittherapie verabfolgt wird, verursacht 9-Fluorcortisol keine wesentliche Einschränkung der Hormonausscheidung.

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Effect of 9-fluorocortisol on adrenocortical function

Summary Investigation of adrenal cortical function during administration of 9-fluorcortisol revealed—in connection with results obtained from the literature—a dose-related inhibition of the secretion of adrenocortical hormones. Adrenal cortical response to exogenous ACTH remains unaffected. An inhibition of hypophyseal ACTH-secretion is therefore assumed, caused by the structure of the synthetic steroid. At low dosage, as applied in long-term treatment, no significant alteration of steroid excretion patterns was observed.

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Astonin-H, Hersteller: Fa. E. Merck A.G., Darmstadt.

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In der Arbeit werden folgende Abkürzungen verwendet: 17-KS=17-Ketosteroide; 17-OH-CS=17-Hydroxycorticosteroide; F=Cortisol=Pregn-4-en-11,17,21-triol-3,20-dion; E=Cortison=Pregn-4-en-17,21-diol-3,11,20-trion; THF=Tetrahydrocortisol=5-Pregnan-3,11,17,21-tetrol-20-on; allo-THF=allo-Tetrahydrocortisol=5-Pregnan-3,11,17,21-tetrol-20-on; THE=Tetrahydrocortison=5-Pregnan-3,17,21-triol-11,20-dion; Andro=Androsteron=5-Androstan-3-ol-17-on; Ätio=Ätiocholanolon=5-Androstan-3-ol-17-on; DHA=Dehydroepiandrosteron=Androst-5-en-3-ol-17-on.

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Herrn Prof. Dr. med. H. Franke zum 60. Geburtstag gewidmet.     

Three-dimensional reconstruction of transmitter-identified central neurons by “en bloc” immunofluorescence histochemistry and confocal scanning microscopy

Summary A new method for three-dimensional reconstruction of transmitter-identified neurons is presented which involves en bloc immunofluorescence histochemistry and confocal scanning microscopy. The technique was applied to different types of neurons in the rat brain and lamprey spinal cord. Thick sections or tissue blocs (50–200 m thick) were incubated with antisera against neuropeptides or monoaminergic markers, followed by fluorescent secondary antibodies. Three-dimensional reconstructions were obtained by scanning the preparations in sequential focal planes with a thin laser beam, while sampling the emitted light in each focal plane. The method is convenient and can be applied to a wide variety of neuron types. The reconstructions obtained are accurate since the optical serial sections of the specimen are perfectly aligned, and optic disturbances such as halo phenomena do not occur.     

Über Fortschritte der Naturwissenschaften und Technik aus der Sicht Eines Klinikers

Ohne Zusammenfassung1. Vorsitzender der Gesellschaft Deutscher Naturforscher und Ärzte 1956/58Festrede aus Anlaß der Eröffnung der 100. Tagung der Gesellschaft Deutscher Naturforscher und Ärzte, Wiesbaden 28. 9. 58.     

The Involvement of Dopamine in Strengthening Cortical Signals Activating NMDA Receptors in the Striatum (a hypothetical mechanism)

A possible mechanism is proposed for the enhancement/weakening of those cortical signals in the cortex-basal ganglia-thalamus-cortex neural network which induce/do not induce opening of NMDA channels in the spiny neurons of the striatum and which can be regarded as strong/weak in terms of this measure. The mechanism is based on the modulatory influences of dopamine on changes in the efficiency of corticostriatal inputs. In the absence of dopamine, relative increases in the intensity of strong (weak) cortical signals can lead to the induction of long-term potentiation (depression) of corticostriatal synapses. In this case, because of the differently directed influences on thalamic cells of signals passing via strionigral and striopallidal cells, strong signals at the output of the thalamus are weakened, while weak signals are strengthened. Activation of dopamine D₁ (D₂) receptors on strionigral (striopallidal) neurons may facilitate increases in the extent of long-term potentiation/depression (decreases in the extent of long-term potentiation/depression or induction of long-term potentiation/depression). The consequence of this is that strong signals at the output of the thalamus can be strengthened synergistically, while weak signals cab be weakened synergistically. Background cortical signals evoking tonic release of dopamine in the striatum can decrease strengthening because of weakening of the modulatory influence of dopamine on the modification of corticostriatal synapses.     

”Reflexes of purpose and freedom” in the comparative physiology of higher nervous activity

The most complex unconditioned reflexes of aim and freedom, discovered by I. P. Pavlov, are compared with the competence drive and the motivation of the resistance to coercion, respectively, described by contemporary ethologists. On the basis of the unconditioned reflex of purpose, conditioned reflexes were developed in which positive emotions arising in connection with the perfection of a skill, irrespective of its pragmatic significance at a given moment, serve as the reinforcement. The unconditioned reflex of freedom is regarded as a phylogenetic precursor of the will, and its acute extinction as the physiological mechanism of hypnosis. It was demonstrated experimentally that the appearance of the state of animal hypnosis (immobilization catatonia) in rabbits is accompanied by the predominance of electrical activity and heat production in the right hemisphere, i. e., by symptoms which are found in hypnosis in man.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 3, pp. 415–420, May–June, 1989.     

Identification and quantitation of cortisol metabolites in rat liver homogenate and -slices

Summary Cortisol-1, 2-H³ was incubated with rat liver homogenate and/or rat liver slices in the presence of a NADPH-generating system. The following metabolites could be identified in adult male rats: -cortol, allo--cortol, 3-allo--cortol, 20-hydroxy-cortisol, 11, 17, 20, 21-tetrahydroxy-5-pregnan-3-one, 3-allotetrahydrocortisol, tetrahydrocortisol, trace amounts of allotetrahydrocortisol and two highly polar metabolites only partly identified. In female rats only tetrahydrocortisol, allotetrahydrocortisol and allodihydrocortisol could be detected in significant amounts.The radioactive metabolites mentioned above were localized and quantitated on paper chromatograms by a 4-radiochromatogram scanner. A nearly perfect correlation was found between these results so obtained and those given by liquid-scintillation counting of each metabolite after its elution from the paper.Part of this work was supported by grant n° 695 of the National Fonds voor Wetenschappelijk Geneeskundig Onderzoek.Stagiair of the Nationaal Fonds voor Wetenschappelijk Onderzoek.     

Die Vergrösserung des funktionellen und absoluten Totraumes und dessen Beziehung zur Gasstoffwechselstörung bei obstruktivem Lungenemphysem

Zusammenfassung Die Bestimmung der verschiedenen Totraumgrößen bei Patienten mit obstruktivem Lungenemphysem gibt die Möglichkeit, die Ursachen für die Vergrößerung des funktionellen Totraumes zu erfassen. Der absolute Totraum ist bei diesen Patienten nur mäßig vergrößert. Die Vergrößerung des Mischluftanteiles und die Entwicklung von Paralleltoträumen wird diskutiert. Als im Vordergrund stehend wird die ungleichmäßige Ventilierbarkeit des Alveolarraumes angesehen, die alle funktionellen Symptome, wie sie bei obstruktivem Lungenemphysem zu beobachten sind, einschließlich des reversiblen arterio-venösen Kurzschlusses erklären kann. Die nach der Bohrschen Formel zu errechnende Vergrößerung des funktionellen Totraumes entspricht nicht der Vergrößerung von Toträumen im anatomischen Sinne. Die Vergrößerung des funktionellen Totraumes ist ebenfalls aus der ungleichmäßigen Ventilation mit dem Auftreten von alveolär-arteriellen Kohlensäuredruckgradienten abzuleiten.     

Susceptibility to beta-lactam antibiotics in septicemia isolates from twenty-nine European laboratories

In 1984 the European Study Group on Antibiotic Resistance (ESGAR) consecutively collected gram-negative bacilli and staphylococci blood isolates and performed susceptibility testing with 11 antibiotics using the microdilution method. In all 2,578 isolates were collected: 68% gram-negative bacilli and 32% staphylococci. The MICs of ampicillin and cefazoline for the susceptible gram-negative bacilli were 1–8g/ml; of piperacillin0.5–4; of Sch 34343, cefotaxime, moxalactam, ceftazidime and aztreonam0.5–2g/ml; of cefoxitin, cefuroxime and cefamandole0.5–8g/ml. For susceptible staphylococci the MICs of cefazoline and cefuroxime were0.5–1g/ml, and of cefoxitin, moxalactam, ceftazidime and cefotaxime,0.5–32 g/ml. The resistance levels varied between laboratories and countries, being lower in Northern Europe. In clinical protocols on patients with gram-negative septicemia from whom cefazoline-resistant strains were isolated, cefotaxime was the beta-lactam most commonly used (12%). In protocols on patients with staphylococcal septicemia from whom gentamicin-resistant or cefazoline-resistant strains were isolated, the most commonly used beta-lactam was cloxacillin (6%).     

Zur flammenphotometrischen Calciumbestimmung im Urin

Zusammenfassung Für die Calciumbestimmung im Urin wird eine einfache und rasche flammenphotometrische Methode ohne vorherige Fällung des Calciums beschrieben. Der Kationenfehler kann dabei durch das Korrekturverfahren weitgehend ausgeschaltet werden, der Phosphat- und Sulfatfehler durch das Parallelverfahren, während der Bicarbonatfehler infolge Ansäuerung entfällt.Der mittlere Gesamtfehler der Methode beträgt etwa ± 7% (± 2).     

Regulation of glycoprotein D synthesis of herpes simplex virus 1 by α 4 protein,the major regulatory protein of the virus,in stably transformed cell lines: effect of the relative gene copy numbers

Summary Earlier studies concerning 1 gene regulation by the 4 protein, the major regulatory protein of herpes simplex virus 1 (HSV-1), in stably transformed cell lines, reported conflicting results, i.e., 4 protein positively regulated the ₁ gB gene in 4/gB cells, while it negatively regulated the ₁ gD gene in 4/BJ cells. Both cell lines were derived from a common parental cell line 4/c 113 that contains 1 copy of the 4 gene, and the only apparent difference between them was the relative copy number of the gB and gD sequences (1 and 30–50, respectively) resident in the cell genome. We investigated this disparity by constructing a cell line (BA 4) that contains one copy each of the 4 and ₁ gD sequences, by fusion of 4/c 113 and BJt cells, containing and expressing respectively 1 copy of the 4 and gD genes. BA 4 cells constitutively expressed both the 4, gD genes inherited from the parental cell lines ( 4/c 113 and BJt). In BA 4 cells the 4 protein positively regulates the gD gene as evidenced from (i) higher levels of gD expression than the parental BJt cells lacking the 4 gene, and (ii) significant decrease in gD expression under conditions that render the 4 protein produced in BA 4 cells non-functional. In addition the ₂gG gene contained within the DNA fragment encoding the gD gene, is also expressed in BA 4 cells. On the basis of these data, we propose that gene regulation by the 4 protein is affected by the relative copy number of these genes, resident in the cell genome.     

Intrakranielle und intraspinale Blutungen unter Behandlung mit Cumarinderivaten

Summary From 1978–1986, 63 patients (48–79 years) under coumarin derivatives had to be hospitalized neurosurgically because of intrcranial or intraspinal bleedings. This corresponds to a twelvefold increased risk compared to the untreated people. The male/female ratio was 1.5. At the time of the bleeding there was no true indication for anticoagulation in at least 60% of the patients. 80% with coma on admission died. Only for 2/7 with an intraspinal hemorrhage the outcome was better than paraplegic. Women proved to have a better chance of survival. — There is a need for more concise indications for chronic anticoagulation.

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Abkürzungen CT Röntgen-Computertomographie - Cumarine für Cumarinderivate; hier zu 97% Phenprocoumon - ZNS-Blutung nur der Kürze wegen fürbegrifflich korrekt: intrakranielle und intraspinale Blutung Meinem Lehrer, Herrn Dr. med. Czeslaw Andrzejewski, zum 70. Geburtstag gewidmet!     

A comparison of isometric force,maximum power and isometric heat rate as a function of sarcomere length in mouse skeletal muscle

The isometric force, maximum power and isometric heat rate have been measured at different sarcomere lengths (SL) between 1.40 and 3.63 m in two types of mouse muscle, soleus and omohyoideus, at 25°C. The SL force relationship is different in the two muscles. At a SL above optimum filament overlap, 2.44 m in omohyoideus muscles, maximum power declined while isometric force remained high. In soleus muscles this occurred above a SL of 2.33 m. In parallel experiments, the isometric heat rate declined linearly with increasing SL above 2.33 m in soleus muscles, while isometric force remained closer to its maximum. At short SL, between 2.33–1.75 m in soleus and 2.44–2.15 m in omohyoideus, maximum power remained at or near its maximum value as did heat rate (soleus) while isometric force fell. In both muscles at SL greater than optimum for force development maximum power output (unlike force) is proportional to filament overlap. The variation in heat rate over this SL range can be described as the sum of a constant rate and a rate proportional to filament overlap. These observations are compatible with the idea that maximum power and heat rate are less affected by non-uniformities in SL than is force.     

The influence of display characteristics on active pursuit and passively induced eye movements

Summary A series of experiments has been conducted on human subjects to examine the effect of the movement of small targets located in the peripheral visual field on oculomotor response. Subjects were presented with either a single centrally positioned target or a pair of targets displaced at angles of ±5°, ±10° and ±20° from centre. Target movement was in the horizontal plane, the paired targets always moving in unison. The stimulus waveform consisted of either a sinusoidal or random target motion encompassing a frequency range from 0.1 to 4 Hz with an angular displacement of ±3.5°. Subjects made two types of response. First they were instructed to follow the single target or the centre point of the paired targets. In this active pursuit condition the gain of slow-phase eye velocity progressively decreased as the moving targets were moved from the central position to the most peripheral location (±20°). Secondly, subjects were required passively to ignore the target movement by staring blankly ahead. During this passive response nystagmic eye movements were induced for which the slowphase eye velocity also decreased with increasing target eccentricity, but the gains were always less than those induced during active pursuit. The frequency characteristics of the passive response were very similar to those of the active response, breaking down at frequencies beyond 1 Hz. The ability to suppress the passive response was also investigated by the presentation of a tachistoscopically illuminated earth-fixed target. The response was found to decline as the interval between presentations of the fixation target was decreased from 3000 ms to 100 ms. It is suggested that the passive response originates from a basic velocity drive to the oculomotor system resulting from image movement across the retina. This velocity drive may be cancelled with adequate fixation but must be enhanced to accomplish desired eye velocity during active pursuit.     

Skull radiograph measurements of normals and patients with basilar impression; use of Landzert's angle

Summary One hundred normal lateral skull radiographs were studied and those of ten patients with basilar impression attending Kenyatta Hospital, Nairobi. The mean shortest distance of the odontoid tip to McGregor's basal line was 1.2±2.28 mm below the basal line (range 6 mm below to 3 mm above basal line), in normals and 9±2.7 mm (6–14 mm) above basal line in patients. The mean basal angle was 113±7 (102–133) in normals and 122±6 (113–125) in patients. The mean nasion-basion-opisthion angle was 162±4 (154–169) in normals and 178±5 (173–185) in patients. The mean total length of clivus was 48±3.7 mm (43–56 mm) in normals and 44±6.6 (36–48 mm) in patients group. The mean median diameter of the foramen magnum was 39±5 mm (30–48 mm), atlas 21±3 mm (18–25 mm) axis 18±3 mm (14–23 mm), third cervical vertebra 16±2 mm (13–22 mm) in normals and in patients: 39±4 mm (36–45 mm), atlas 23±6 (l5–30 mm) axis 19±4 mm (16–25 mm), third cervical vertebra 16±3 (14–20). There was a significant difference in the position of the odontoid tip and the nasion-basion-opisthion angle between the normal and patient groups. All the other parameters measured in this work did not differ significantly between the two groups.

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Etude anatomo-radiologique de crânes normaux et de crânes pathologiques avec impression basilaire; utilisation de l'angle de Landzert

Résumé Cent crânes normaux ont été étudiés sur des radiographies de profil ainsi que dix crânes pathologiques présentant des impressions basilaires chez des patients traités à l'HÔpital Kenyatta de Nairobi. La plus courte distance moyenne entre le sommet de l'odontoÏde et la ligne basale de McGregor a été de 1,2±2,28 mm au-dessous de la ligne basale (extrÊmes étendues de 6 mm au-dessous à 3 mm au-dessus de la ligne basale), chez les sujets normaux et de 9±2,7 mm (6–14 mm) au-dessus de la ligne basale chez les sujets pathologiques. L'angle basai moyen était de 113±7 (102–133) chez les sujets normaux et 122±6 (113–125) chez les sujets pathologiques. L'angle moyen nasion-basion-opisthion était de 162±4 (154–169) chez les sujets normaux et 178±5 (173–185) chez les sujets pathologiques. La longueur moyenne totale du clivus était de 48±3,7 mm (43–56 mm) chez les sujets normaux et 44±6,6 (36–48 mm) chez les sujets pathologiques. Le diamètre moyen du foramen magnum était de 39±5 mm (30–48 mm), celui du foramen vertébral de l'atlas était de 21±3 mm (18 à 25 mm), celui de l'axis (18±3 mm (14–23 mm), celui de la troisième vertèbre cervicale: 16±3 mm (13–22 mm) chez les sujets normaux; chez les sujets pathologiques les chiffres étaient les suivants: foramen magnum 39±4 mm (39–45 mm), atlas 23±6 (15–30 mm), axis 19±4 mm (16–25 mm), troisième vertèbre cervicale 16±3 mm (14–20 mm). Il existe une différence significative dans la position du sommet de l'odontoÏde et la valeur de l'angle nasion-basion-opisthion entre les deux groupes. Aucun des autres paramètres mesurés dans ce travail ne présentait de différence significative entre les deux groupes.

     

Immunologische Untersuchungen an heterogen zusammengesetzten Plasmocytom-γ-Globulinen

Zusammenfassung Durch Kombination der Stärkegel-Elektrophorese mit immunologischen Techniken (Stärkegel-Immunoelektrophorese und Doppeldiffusionsversuche) ist es möglich, das -Globulin des Normalserums und des Plasmocytoms näher zu differenzieren. Zunächst kann festgestellt werden, daß das -Globulin anodenwärts bis in den Bereich der Haptoglobine wandert. Kleinmolekulare -Globulinkomponenten wie das Bence-Jones-Protein können die Beweglichkeit des Transferrins besitzen und hier durch Präcipitation in der Stärkegel-Immunoelektrophorese nachgewiesen werden.Die einzelnen Subfraktionen des Plasmocytom--Globulins sind mit dem normalen -Globulin antigenverwandt, aber nicht identisch. In den Doppeldiffusionsversuchen, die sich in der Kombination Stärkegel/Agargel durchführen lassen, zeigt sich, daß auch die Paraproteinkomponenten, deren elektrophoretische Beweglichkeit von der des normalen 7S -Globulin abweicht, mit Immunserum gegen -Globulin präcipitiert werden. Unter den Präcipitaten lassen sich die des normalen und des abnormen -Globulins unterscheiden. Mit dem hier verwandten Anti--Globulinserum reagierten die Paraprotein-Subfraktionen gleichartig; es ist aber möglich, daß sich bei Verwendung individualspezifischer Immunseren oder Immunseren gegen einzelne Subfraktionen Unterschiede der Antigenstruktur fassen lassen.II. Teil der 1962 mit dem Theodor-Frerichs-Preis der Deutschen Gesellschaft für Innere Medizin ausgezeichneten Untersuchungen. I. Teil: Z. Naturforschg.17b, 598 (1962)II. Teil der 1962 mit dem Theodor-Frerichs-Preis der Deutschen Gesellschaft für Innere Medizin ausgezeichneten Untersuchungen. I. Teil: Z. Naturforschg.17b, 598 (1962).     

Spontaneous and agonist-induced openings of an acetylcholine receptor channel composed of bovine muscle α-, β and δ-subunits

During the development of mammalian muscle the -subunit of the nicotinic acetylcholine receptor (AChR) is replaced by the -subunit to produce well-defined alterations in the conductance and gating of the channel. To gain a better unterstanding of the functional role of the and -subunits, we have studied the properties of an AChR channel lacking these subunits. The AChR expressed in Xenopus oocytes injected with the bovine -, and -subunit-specific mRNAs (referred to as -AChR) is unusual in that its channel opens spontaneously at a high frequency in the absence of agonist. From a comparison of the -AChR with complete receptors containing either the or -subunit, we conclude that the and -subunits influence most channel properties, including agonist binding, and are especially important for stabilizing the closed state of the unliganded receptor channel. The -AChR can form when a complete set of four subunit-specific mRNAs is injected. The ease with which it is assembled raises the possibility that the - AChR contributes to some of the variations in receptor properties that occur during development.