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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The nicotinic acetylcholine receptor (AChR) exhibits at least four different conformational states varying in affinity for agonists such as acetylcholine (ACh). Photoaffinity labeling has been previously used to elucidate the topography of the AChR. However, to date, the photosensitive probes used to explore the cholinergic binding site photolabeled only closed or desensitized states of the receptor. To identify the structural modifications occurring at the ACh binding site on allosteric transition associated with receptor activation, we have investigated novel photoactivatable 4-diazocyclohexa-2,5-dienone derivatives as putative cholinergic agonists. Such compounds are fairly stable in the dark and generate highly reactive carbenic species on irradiation. In binding experiments using AChRs from Torpedo marmorata, these ligands had affinities for the ACh binding site in the micromolar range and did not interact with the noncompetitive blocker site (greater than millimolar affinity). Irreversible photoinactivation of ACh binding sites was obtained with the ligand 1b (up to 42% at 500 µM) in a protectable manner. In patch-clamp studies, 1b was shown to be a functional agonist of peripheral AChR in TE 671 cells, with the interesting property of exhibiting no or very little desensitization even at high concentrations.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Prostaglandins 47 (1994), S. 353-365 
    ISSN: 0090-6980
    Keywords: Ca current ; Prostaglandins ; patch clamp ; rat oarta ; smooth muscle cell ; vasodilation
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 394 (1982), S. 202-210 
    ISSN: 1432-2013
    Keywords: Fast and slow muscle fibres ; Synaptic currents ; Cholinesterase inhibitors ; Potential dependency ; Voltage clamp ; ACh-induced noise ; Frogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Miniature end-plate currents (mepcs) were recorded from fast and slow muscle fibres in two muscles, m. cruralis and m. ileofibularis, under voltage clamp or extracellularly. Both fibre types showed an identical sensitivity to α-bungarotoxin, and an exponential dependence of mepc decay time-constant upon membrane potential, but there were some important differences: i) the rise time and half-time of decay were approximately 3 times longer in slow junctions than in fast ones: ii) inhibition of AChE had a more prominent effect on mepcs recorded in fast fibres while preserving the significant difference in mepc time course between fast and slow fibres; iii) treatment by α-bungarotoxin had a greater effect on mepc time course in slow junctions even in the absence of anticholinesterase; iv) a more prominent variability of mepc time course was observed in slow junctions, especially after treatment by anticholinesterase drugs. Fluctuations of conductance of the postjunctional membrane induced by application of acetylcholine to different frog muscle fibres have been analysed. The autocorrelation function of these fluctuations was exponential and gave information about the mean life-time of single ionic channels and their conductance. There were two main classes of ionic channels: “fast” with mean life-time 2.9 ms and conductance 18.3 pS in single-innervated fast muscle fibres of phasic bundle of m. ileofibularis, m. sartorius and m. cutaneous pectoris; and “slow” −8.3 ms and 12.5 pS correspondingly (t=8–10°C, holding potential −80 mV) in multi-innervated fibres of tonic bundle of m. ileofibularis. An intermediate type of singly-innervated muscle fibres was found in tonic bundles of m. cruralis and m. ileofibularis. The time course of mepcs and life-time of ionic channels recorded in these fibres were intermediate between typical fast and slow mepcs. Simultaneous analysis of mepcs and ACh-induced current fluctuations suggests that the decay of mepcs in typical fast fibres is governed mainly by the closing of ionic channels while the decay of most mepcs in slow fibres is substantially slower than the rate of channel closing. Evidently some additional factors may prolong the effect of ACh-quanta in slow junctions. The relationship between the functional properties of different muscle fibres and rates of sequential steps of postjunctional activation is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-8205
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Neuroscience and behavioral physiology 4 (1970), S. 63-73 
    ISSN: 1573-899X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 1. Responses of two extreme types of neurons in the inferior colliculus of rats to acoustic stimuli of rising amplitude are described. Neurons of group I are characterized by a decrease in the number of spikes in the response, an increase in the latency, and small changes in threshold as the rise time of noise or the optimal frequency increases. Group II neurons are characterized by preservation of the original response of one or two spikes, slight changes in latency, and a sharp increase in threshold when the rise time of the stimulus (noise, optimal and nonoptimal frequencies) increases. 2. For stimuli with rising amplitude the sharpness of the frequency-threshold curves of group I neurons increases because of a sharp increase in threshold to nonoptimal frequencies and no change in threshold to optimal frequencies. The sharpness of the frequency-threshold curves of group II neurons is unaltered, and thresholds to all acoustic frequencies are increased with a decrease in the steepness of rise of the stimuli.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Neurophysiology 16 (1984), S. 443-452 
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Parameters of single acetylcholine-activated ionic channels and the time course of miniature end-plate currents (MEPC) were compared in experiments on fast and slow lamprey, frog, chicken, and rat muscle fibers. The mean open time of the channels was shown to be the principal, but not the only factor determining the duration of MEPC. The role of the remaining factors and, in particular, of insufficiency of acetylcholinesterase activity, in slow muscle fibers and also in "giant" MEPC generation, is much greater than in fast fibers or during ordinary MEPC generation. Relatively low acetylcholinesterase activity favors asynchronous interaction between acetylcholine molecules and receptors, which delays the time course of synaptic responses. Mechanisms of acceleration of MEPC decay under the influence of α-bungarotoxin and D-tubocurarine, and also the conditions for MEPC generation in different regions of the neuromuscular junction are discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Neurophysiology 20 (1988), S. 289-295 
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From analyzing the mathematical model of miniature endplate current (MEPC) generation described previously an optimal set of parameters was found providing the best match between the results of stimulation and experimentally obtained findings. The time course of MEPC in the controls, after cholinesterase inhibition, and following a bungarotoxin-induced reduction in the density of unoccupied cholinoreceptors were described within the framework of the model. This model also statisfactorily describes voltage-dependent current decay, and the currentvoltage relationship of MEPC, as well as the kinetics of “giant” MEPC observed during cholinesterase inhibition. The influence of the parameters of the model on “model” MEPC is also examined. The good match between the results of modelling and experimental findings leads to the conclusion that the model gives a true picture of different processes contributing to the generation of MEPC.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Neurophysiology 21 (1989), S. 26-31 
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Currents passing through individual potassium channels with anomalous (inward) rectification were recorded at the neuronal membrane ofPlanorbarius corneus using the patch clamp technique. These currents could be detected, whether in "right side out" or "inside out" configurations in the presence of 50 mM potassium ions or one of the potassium channel blockers: tetraethylammonium (TEA), barium, or cesium (2–20 mM) on the external side of the membrane. Inward currents were observed in individual channels at potentials more negative than level of potassium equilibrium potential (Ek); conductance of these measured 81±12 pS (n=11). At more positive potentials than Ek, conductance fell to zero. Potassium channels with anomalous (inward) rectification inPlanorbarius corneus resemble equivalent channels in other cells in their kinetics: time scale of the open state may be described by a single exponential function. This would imply that the ionic channel has a single open state. Time scale of the closed state was biexponential, thus indicating the possible existence of two kinetically different nonconducting states of the potassium channel with anomalous (inward) rectification at the neuronal membrane ofPlanorbarius corneus.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A mathematical model of the effects of open (ionic) channel blockers on generation of postsynaptic current at the neuromuscular junction is described. Quantitative aspects of simple blocking action are analyzed as well as criteria by which blockade of ionic channels may be discriminated from modification of their activation kinetics. Results of simulation are compared with experimental data. Some effects of channel-blocking substances following cholinesterase inhibition are examined.
    Type of Medium: Electronic Resource
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  • 10
    Publication Date: 2013-07-23
    Description: Aims To determine the role of gap junctions (GJs) in hypoxic pulmonary vasoconstriction (HPV). Methods and results Studies were performed in rat isolated intrapulmonary arteries (IPAs) mounted on a myograph and in anaesthetized rats. Hypoxia induced a biphasic HPV response in IPAs preconstricted with prostaglandin F 2α (PGF 2α , 3 µM) or 20 mM K + . The GJ inhibitors 18β-glycyrrhetinic acid (18β-GA, 30 µM), heptanol (3.5 mM), or 2-aminoethoxydiphenyl borate (2-APB) (75 µM) had little effect on the transient Phase 1 of HPV, but abolished the sustained Phase 2 which is associated with Ca 2+ sensitization. The voltage-dependent Ca 2+ channel blocker diltiazem (10 µM) had no effect on HPV, and did not alter the inhibitory action of 18β-GA. Sustained HPV is enhanced by high glucose (15 mM) via potentiation of Ca 2+ sensitization, in the presence of high glucose 18β-GA still abolished sustained HPV. Simultaneous measurement of tension and intracellular Ca 2+ using Fura PE-3 demonstrated that whilst 18β-GA abolished tension development during sustained HPV, it did not affect the elevation of intracellular Ca 2+ . Consistent with this, 18β-GA abolished hypoxia-induced phosphorylation of the Rho kinase target MYPT-1. In anaesthetized rats hypoxia caused a biphasic increase in systolic right ventricular pressure. Treatment with oral 18β-GA (25 mg/kg) abolished the sustained component of the hypoxic pressor response. Conclusion These results imply that GJs are critically involved in the signalling pathways leading to Rho kinase-dependent Ca 2+ sensitization during sustained HPV, but not elevation of intracellular Ca 2+ , and may explain the dependence of the former on an intact endothelium.
    Print ISSN: 0008-6363
    Electronic ISSN: 1755-3245
    Topics: Medicine
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