The genetics of type A potassium channels in Drosophila melanogaster.
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Animals↗
Biomedical subjects
A Mallart
Publications and source records attributed to A Mallart.
Placental metastasis from maternal bronchial oat cell carcinoma.
We describe the case of a young pregnant woman with oat cell carcinoma diagnosed by immunohistochemical reactions and ultrastructural study of a mediastinal biopsy specimen. A neonate was delivered by a cesarean section without evidence of carcinoma, but a thorough pathologic examination of the placenta showed intervillous metastasis of the maternal oat cell carcinoma. This case is interesting, since placental metastases from solid tumors are rare (38 reported cases with pathologic examination of the placenta), and 39% of them arise from maternal melanomas.
Adult↗
The mode of action of guanidine on mouse motor nerve terminals.
The action of guanidine on presynaptic membrane currents has been investigated to elucidate its facilitatory effect on phasic transmitter release at the mouse neuromuscular junction. Guanidine (2-10 mM) produced a near complete inhibition of the fast voltage-dependent K current. This effect is expected to allow an increase in Ca2+ influx and, thereby, in transmitter release upon nerve stimulation. Guanidine failed to block the Ca-dependent K current of the nerve terminals.
Animals↗
Potassium channel blockers and impulse propagation in murine motor endplate disease.
An electrophysiologic study has been performed on motor nerves of mice affected with hereditary "motor endplate disease" (MED). Bath application of potassium channel blockers, such as tetraethylammonium and 3,4-diaminopyridine, which are almost without effect on the monophasic compound action potential of normal nerves, considerably enhanced the action potential duration in nerves from mutant mice. Furthermore, external current recordings from motor endings revealed an absence of the K-dependent waveform component in MED mice, which indicates a similar K current intensity in the terminal part of the endings and in the heminode. These observations suggest that in the mutant, unlike in normal mice, K channels play a role in action potential electrogenesis. Possible relationships with paranodal dysmyelination are discussed.
4-Aminopyridine↗
An electrophysiological study of skeletal muscle fibres in the 'muscular dysgenesis' mutation of the mouse.
Experiments were performed on muscles of 18-19 day mice fetuses affected with muscular dysgenesis (mdg). Action potentials generated by electrical stimulation or potassium depolarization failed to trigger muscle contraction in mdg muscle fibres. By contrast, muscle contraction could be obtained by caffeine (15 mM) and, to a lesser degree, by nerve stimulation. We conclude that a defect in excitation-contraction (E-C) coupling is the cause of muscle paralysis. An early after potential (EAP) was present in the decay phase of the action potential and a potential 'creep' occurred in response to hyperpolarizing current pulses which can be taken as evidence for the presence of T-tubules in mdg muscle fibres. Data obtained from square pulse analysis and EAP measurements indicate larger input impedance and membrane time constant in mdg as compared to controls, which contrasts with similar surface membrane time constant (as estimated from the foot of the action potential) in both types of muscle. The excitability of the T-tubule system was tested by recording action potentials at early stages of TTX (5 X 10(-7) M) perfusion or washout in mdg and control muscles. In both cases, the action potentials decreased in amplitude and rate of rise and displayed two peaks, the second of which was suppressed by detubulation using the formamide treatment. This indicates action potential generation in the T-tubule membrane of mdg muscles. In all the impaled muscle fibers, nerve stimulation evoked epps which were accompanied by a weak local contraction in relation with Ca2+ influx through postsynaptic channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Two distinct calcium-activated potassium currents in larval muscle fibres of Drosophila melanogaster.
The non-synaptic membrane currents of muscle fibres have been studied in late embryogenesis of Drosophila melanogaster using the voltage-clamp technique in wild-type and Shaker mutant third instar larvae. Five currents were found in the wild type muscle membrane at this embryonic stage: one fast inward Ca current (ICa), two fast outward K currents (IA and IAcd) and two slow outward K currents (IK and IC). IAcd and IC are Ca-dependent. Several procedures were used to separate IAcd from IA: IAcd is present in Shaker mutants which are characterized by the absence of IA (Salkoff and Wyman 1981); IAcd, but not IA, is suppressed by Co2+ (10 mM) or La3+ (1 mM); IAcd shows steady-state inactivation at more positive potentials than IA; IAcd, unlike IA, is 3,4-diaminopyridine (3,4-DAP) resistant. Furthermore, tetraethylammonium (TEA, 20 mM) which is known to be uneffective on IA, blocks IAcd. IAcd could not be triggered by using strontium or barium as calcium substitutes. By partial substitution of Ca by Ba or Sr ions, it was found that Ba, but not Sr, blocks the IAcd channel. A non-inactivating, TEA sensitive, Ca-dependent K current (IC), which gave N-shaped I-V plots, could be separated from IK by using Ca-channel blockers. IC and IK activate at membrane potentials of about -25 mV and -10 mV, respectively. The participation of IAcd and IC to membrane electrophysiology is discussed.
Animals↗
[Allergens of animal origin].
Dander's Allergy still is an actual problem. In urban population the incidence increase with proliferation of domestic Animals in Houses, when, in rural population, cows and horses sensibilization frequency decrease with present evolution of farming. The newness is represented by the amelioration of knowledge in last years of biochemical nature of Antigens and the identification of major allergens.
Allergens↗
Differential effects of alpha-latrotoxin on mouse nerve endings and fibers.
The action of alpha-latrotoxin (alpha-LTx), the major toxic component from black widow spider venom, was studied on mammalian motor nerve endings and fibers. Electrophysiologic recordings of presynaptic and postsynaptic responses at early stages after the application of different doses of alpha-LTx showed massive transient increases in transmitter release and changes in the configuration of presynaptic currents. Later, a loss of invasion of terminals by nerve impulses occurred, whereas the impulse conduction in nerve fibers was unmodified. These results support the idea of a selective effect of alpha-LTx on presynaptic membrane excitability.
Action Potentials↗
Effects of Anemonia sulcata toxin II on presynaptic currents and evoked transmitter release at neuromuscular junctions of the mouse.
The effect of Anemonia sulcata toxin II (ATX-II) on the amount of transmitter released by nerve impulses was investigated in motor end-plates of the mouse. ATX-II (80 nM) caused repetitive end-plate potentials in response to a single nerve stimulus and a 3- to 4-fold increase in the quantal content of the phasic end-plate potential. This increase is less than what would be expected if ATX-II induced plateau action potentials at the motor endings. To solve this discrepancy presynaptic currents were recorded by focal extracellular electrodes. It was found that the K current present at the endings is strong enough to prevent the development of presynaptic plateau action potentials, in contrast to what has been observed in other excitable membranes (unmyelinated axons, nodes of Ranvier and skeletal muscle fibres). By using tetraethylammonium and 3,4-diaminopyridine to block K channels and Co2+ to block Ca channels, ATX-II allowed the development of prolonged plateau responses at the endings upon motor nerve stimulation. These results suggest that the mouse motor endings are endowed with a relatively powerful K channel system, which effectively controls the amount of presynaptic depolarization.
Animals↗
Electrical activity of mouse motor endings during muscle reinnervation.
An in vitro study of electrical activity of regenerating motor endings was performed 11-15 days after the crushing of one motor nerve supplying the triangularis sterni muscle in the adult mouse. For this purpose, presynaptic membrane currents elicited by electrical stimulation of the regenerating nerve were recorded by external electrodes. Ionic channel distribution along the length of the endings was deduced from wave form configuration in normal perfusing fluid together with changes produced by application of specific channel blocking agents. The sharp negative deflection which was shown to correspond to inward Na+ current by its sensitivity to tetrodotoxin application could be recorded along most of the length of the endings indicating a widespread distribution of Na channels. Frequent absence of the late wave form component which signals K+ current was taken to indicate an even K+ current density in the few last nodes, the heminode and the distal part of the endings. Therefore, it appears that regenerating motor endings are characterized by an overlap of Na and K conductances all along their length. In the course of regeneration, the heminode loses the sensitivity to K channel blocking agents and the remainder of the terminal becomes insensitive to tetrodotoxin, the former change occurring usually earlier than the latter.
4-Aminopyridine↗
Electric current flow inside perineurial sheaths of mouse motor nerves.
Micro-electrodes were inserted inside the perineurial space to record external currents along the superficial nerve bundles of the triangularis sterni muscle of the mouse upon motor nerve stimulation. Two kinds of external currents were distinguished, the first circulating between neighbouring nodes of Ranvier in each fibre and the second circulating between the nodes and the motor endings. Ending-node current was caused by differences in the time course and the amplitude of the potential change at the endings and at the nodes, which depended in turn, on differences between their respective membrane conductances. The stretch of nerve over which ending-node current extended served to estimate that about eight to ten nodes of Ranvier supply the motor endings with depolarizing current.
Action Potentials↗
A calcium-activated potassium current in motor nerve terminals of the mouse.
Local circuit currents involving presynaptic terminals were recorded by micro-electrodes inserted into the perineurium of nerves from the triangularis sterni muscle of the mouse. A transient outward current component was isolated by blocking the voltage-activated (delayed rectifier) K current by 3,4-diaminopyridine (3,4-DAP). The amplitude of this component depended on external K concentration and fell to zero at [K]o = 15 mM. Since it also depended on [Ca]o, it was identified as a Ca-activated K current (IK(Ca)). Tetraethylammonium (TEA) (2 mM), Ba (2 mM), Co (10 mM) and Mn (2.5 mM) blocked IK(Ca). IK(Ca) decayed to zero in approximately 12 ms and recovered from inactivation in about 100 ms. Ca current was enhanced in inverse proportion to the degree of IK(Ca) depression. The possible role of IK(Ca) in the process of neuromuscular facilitation is briefly discussed.
4-Aminopyridine↗
Ionic channel distribution in regenerating mouse motor endings.
One of the nerves supplying the Triangularis sterni muscle of the adult mouse was crushed and focal extracellular recordings were made from the regenerating motor nerve terminals. Stimulation of the nerve elicited 4 types of signals depending upon the position of the electrode along the newly formed terminal branches. Specific ionic channel blockers were applied in the bath or iontophoretically to identify the nature of the different signal components. Sodium and potassium channels appeared to be located along most of the length of the newly formed terminals. This overlapping distribution differs considerably from their segregated localization previously described for mature endings. During maturation of regenerating endings, potassium channels disappear from the heminodal area and the density of sodium channels is greatly reduced along the remainder of the branches. Presynaptic evidence for polyneuronal reinnervation of single endplates is presented.
Animals↗
Presynaptic currents in frog motor endings.
Membrane currents were recorded from non-myelinated frog endings by external electrodes. Changes in shape of the signals recorded at varying distances from the myelin end could be explained by assuming a non uniform distribution of Na and K channels along the presynaptic terminal. Specific channel blocking agents revealed that Na channels are present in highest density in the first half of each terminal branch and at almost undetectable levels near the extreme end, while K channels show a more widespread distribution with higher density at medial parts. Suppression of K conductance revealed Ca current which was seen as outward current near the myelin end.
4-Aminopyridine↗
Secretion of a chemotactic factor for neutrophils and eosinophils by alveolar macrophages from asthmatic patients.
The studies presented in this article demonstrate the release of an IgE-dependent chemotactic factor for polymorphonuclear neutrophils (PMN) and eosinophils by alveolar macrophages (AMs) from normal subjects (n = 15) and allergic asthmatic patients (n = 15). A 60-minute incubation of normal AMs previously sensitized by 20% nonheated allergic sera with anti-human IgE antibody or the related allergen induced the release of a chemotactic activity (CA) for PMN and eosinophils in culture supernatants. When AMs were obtained from asthmatic patients, direct incubation with anti-IgE or the related allergen induced the same CA, whereas incubation with an unrelated allergen failed to produce CA (neutrophil CA after addition of anti-IgE, 22.5 +/- 3.5 cells per high power field; with related allergen, 15.8 +/- 3.6; with unrelated allergen, 0.7 +/- 1.8; p less than 0.0001). A partial characterization of the neutrophil chemotactic factor was carried out. Enzymatic treatment by trypsin or carboxypeptidase or by heating (56 degrees C for 3 hr) failed to abolish the neutrophil CA. After gel filtration the greater part of the neutrophil CA (80%) was recovered among low-molecular-weight components (300 to 1300 daltons). A preliminary deactivation of PMN by leukotriene B4 suppressed the CA of AM supernatants. These results indicate that IgE-dependent stimulation of AMs produces a neutrophil and eosinophil CA, present in a low-molecular-weight fraction possibly related to leukotrienes, and emphasizes the role of AMs in inflammatory lung processes during allergic asthma.
Adult↗
Botulinum A toxin and tetanus toxin do not affect presynaptic membrane currents in mammalian motor nerve endings.
The hypothesis according to which BoTx and TeTx block neuromuscular transmission by impairing Ca2+ influx was tested by recording presynaptic membrane currents at motor endplates of the mouse by means of external electrodes. The use of K-channel blockers allowed us to observe inward Ca current which was unaffected by bath application of BoTx or TeTx at doses which block neuromuscular transmission.
Animals↗
Electrophysiological and morphological studies of a motor nerve in 'motor endplate disease' of the mouse.
Motor nerves of mice affected with hereditary 'motor endplate disease' were examined by means of electrophysiological and morphological techniques. Conduction velocity was slower, the refractory period was prolonged and the temperature sensitivity higher in mutants as compared to controls of the same age. Most of the axons examined in the electron microscope showed signs of paranodal demyelination. The relationship between the morphological and the electrophysiological findings is discussed. We conclude that alterations in the motor axons can account for the failures in neuromuscular transmission described previously in the med mutation.
Animals↗
Presynaptic currents in mouse motor endings.
1. We used external electrodes placed under precise visual control on motor endings of the mouse to record electrical activity promoted by nerve stimulation.2. Three types of wave form have been observed in relation to well-defined electrode emplacements: (i) at the transition between myelinated and non-myelinated parts of the axon, the wave form consists of two negative deflexions preceded by a small positivity (preterminal response), (ii) at the main part of the terminal branches, we obtained a two component positive wave form (terminal response) and (iii) electrode positions in a narrow area between the former and the latter yielded triphasic (positive-negative-positive) wave forms (intermediate responses).3. Since these responses could not be readily interpreted in terms of classical description of membrane currents associated with propagating action potentials, we used specific channel blocking agents to identify wave form components.4. Bath application of tetraethylammonium or aminopyridines, or, better, a combination of both, suppressed delayed positive deflexions of terminal and intermediate responses and the late negative component of preterminal responses. Local inophoretic drug application showed that K channels are present only at the terminal part of the endings. K(+) outflux promotes a local circuit whose sink is located at the preterminal part where it generates the late negative deflexion of the preterminal response.5. Local application of tetrodotoxin suppressed the first negative component of preterminal responses but failed to affect electrical activity at the terminal part of the endings. This indicates that Na channels, and, therefore, action potential generation, are restricted to the preterminal part.6. Suppression of K conductance revealed a slow inward current at the terminal part of the endings which could be identified as a Ca current. Ba(2+) and Sr(2+) could substitute for Ca(2+) as inward current carriers.7. Activation of spatially separated Na channels, on one side, and of K and Ca channels, on the other, generated ionic currents and separated local circuit currents which flow between preterminal and terminal parts (and vice versa). Thus, the signals recorded at each point of motor endings correspond to the sum of ionic and passive currents entering (or leaving) the membrane at that point.8. The present results represent a further example of heterogeneity of axonal membrane.
Action Potentials↗