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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Linopirdine is a cognition enhancer which augments depolarization-induced transmitter release in the cortex and which is under consideration for potential treatment of Alzheimer's disease. It has previously been reported to inhibit M-type K+ currents in rat hippocampal neurons. In the present experiments we have tested its effect on whole-cell M-currents and single M-channels, and on a range of other membrane currents, in dissociated rat superior cervical sympathetic ganglion cells. Linopirdine inhibited the whole-cell M-current with an IC50 of 3.4 μM and blocked M-channels recorded in excised outside-out membrane patches but not in inside-out patches. This suggests that linopirdine directly blocks M-channels from the outside. It was much less effective in inhibiting other voltage-gated potassium currents [delayed rectifier (IK(v)), IC50 63 μM; transient (IA) current, IC50 69 μM] and produced no detectable inhibition of the fast and slow Ca2+-activated K+ currents Ic and IAHP or of a hyperpolarization-activated cation current (IQ/Ih), at 10–30 μM. However, it reduced acetylcholine-activated nicotinic currents and GABA-activated Cl- currents with IC50 values of 7.6 and 26 μM respectively. It is concluded that linopirdine shows some 20–fold selectivity for M-channels among different K+ channels but can also block some transmitter-gated channels. The relationship between M-channel block and the central actions of linopirdine are discussed.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 398 (1983), S. 169-171 
    ISSN: 1432-2013
    Keywords: Nicotinic ACh receptor ; Ganglion-blocking agents ; Channel-blocking activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The actions of bis-ammonium compounds (BAC) on the ionic channels activated by acetylcholine (ACh) were studied in voltage-clamped neurones of rabbit isolated superior cervical ganglion. The kinetics of binding of BAC to open channels was estimated from shortening of the decay of fast excitatory postsynaptic current. The kinetics of dissociation of BAC from open channels was estimated from the kinetics of restoring of second response to double-pulse application of ACh in presence of BAC. The ganglion-blocking activities of BAC correlated with the rate constants of their binding to open channels. It was concluded that delective ganglion-blocking actions of BAC were determined by their channel-blocking activities.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: UTP ; ATP ; Nucleotides ; M-currents ; K currents ; Neuroblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A phospholipase-C-linked nucleotide receptor, sensitive to both uridine and adenosine triphosphate (UTP and ATP) has been cloned from NG108-15 neuroblastoma × glioma hybrid cells. We have tested whether activation of this receptor could inhibit the voltage-dependent K+ current [I K(M) or “M-current”] in NG108-15 cells recorded using whole-cell patch-clamp methods. Both UTP and ATP inhibited I K(M) by 44% and 42%, respectively, at 100 μM. Mean IC50 values were: UTP, 0.77±0.27 μM; ATP, 1.81±0.82 μM. The order of nucleotide and nucleoside activity at 100 μM was: UTP = ATP 〉 ATP[γS] = ITP 〉 2 MeSATP 〉 ADP = GTP ≫ AMP-CPP, adenosine, where ATP[γS] is adenosine 5′-O-(3-thiotriphosphate), ITP is inosine 5′-triphosphate, 2-MeSATP is 2-methylthio ATP and AMP-CPP is α,β methylene ATP. This rank order accords with their activities at the cloned P2U receptor. Effects were not inhibited by suramin (up to 500 μM) or by pre-incubation for 12 h in 500 ng·ml−1 Pertussis toxin. Inhibition of IK(M) was frequently preceded by a transient outward current, probably a Ca2+-activated K+ current, responding to Ca2+ mobilization. No effect on the delayed rectifier K+ current was observed. These observations match those expected from stimulating other phospholipase-C-linked receptors in NG108-15 cells.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 437 (1998), S. 161-163 
    ISSN: 1432-2013
    Keywords: Key words After-hyperpolarization ; Calcium-activated potassium channel ; Hippocampal pyramidal neurones ; Intracellular calcium ; Potassium channel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Small (SKCa) Ca2+-activated K+ channels were identified in membrane patches excised from cultured CA1-CA3 pyramidal neurones of the neonatal rat hippocampus. When recorded in low-K+ extracellular solution ([K+]o=2.5 mM), SKCa channels had a low conductance (@3 pS at 0 mV), were activated by ≥175 nM Ca2+ (P o=0.54 at 500 nM Ca2+) and there were two open-time components (2.1 and @70 ms) to their activity. These properties of single SKCa channels are similar to those of slow after-hyperpolarization channels (sAHP) previously inferred from fluctuation analysis of the sAHP current. It is concluded that the SKCa channel reported here may be the channel that generates the sAHP in hippocampal pyramidal neurones.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acetylcholine-induced membrane conductance was investigated in superior cervical ganglion neurons using a patch-clamp technique. It was found that hyperpolarization and depolarization produce an increase and a reduction in acetylcholine (ACh) conductance. This reduction was unconnected with either reversal of the current induced by iontophoretic ACh application or the presence of Ca ions in the external solution. The time constant of relaxation (τr) of this current, produced by a jump in membrane potential, was found to increase e-fold when the membrane was hyperpolarized by 70 mV, matching the voltage dependence of ACh conductance. This led to the hypothesis that voltage-dependent ACh-induced conductance is entirely determined by the voltage dependence of nicotinic receptor channel gating kinetics.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The action of ionotophoretic application of acetylcholine and serotonin (5-hydroxytryptamine) on neurons of the isolated rabbit superior cervical ganglion was investigated by intracellular recording. The soma of neurons in the ganglion was shown to have no muscarinic receptors and to have only nicotinic receptors scattered irregularly over the whole surface of the neuron soma membrane. Acetylcholine has an excitatory action on presynaptic endings. In about half of the neurons of the ganglion the soma was shown to possess serotonin receptors.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Currents evoked by iontophoretic applications of acetylcholine and postsynaptic currents evoked by single stimulation of the cervical sympathetic nerve were recorded in neurons of the isolated rabbit superior cervical ganglion with membrane voltage clamped and muscarinic acetylcholine receptors blocked by atropine (10−6 M). The α-neurotoxins from snake venom (α-bungarotoxin and α-cobratoxin) in a concentration of 10−6 M caused an increase in amplitude (potentiation) of the acetylcholine current, inhibition of that current, or initial potentiation followed by inhibition, in different neurons. Spectral analysis of the fluctuations of this current showed that α-neurotoxins affect neither the current through a single channel nor the duration of the open state of long-living channels (evidently extrasynaptic), but they approximately double the duration of the open state of long-living channels. This last effect in all probability causes potentiation of the acetylcholine current. The α-neurotoxins also depressed the amplitude of the postsynaptic current evoked by sympathetic nerve stimulation (on average by 44%) and lengthened its decline (on average by 24%). It is postulated that α-neurotoxins may both block and modify activity of the receptor-channel complex in the neurons tested, lengthening the duration of its open state. This latter mechanism of action of α-neurotoxins is exhibited only in long-living channels, evidence that the phamacological properties of the two populations of channels connected with nicotinic acetylcholine receptors are not identical.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of tubocurarine (TC) on current induced by acetylcholine (ACh) in neurons of rat upper cervical ganglia were investigated using techniques for voltage-clamping at the membrane. Reinforcement of TC-induced blockade was achieved by paired application of ACh following prior activation of nicotinic cholinoreceptors, indicating that TC blocked the channels opened by ACh. On average, the TC-open channel complex persisted for 9.8±0.5 sec (n=7) at −50 mV and 20–24°C. It was found that τ increases exponentially with hyperpolarization at the membrane (a shift in membrane potential of 61 mV corresponds to an e-fold change). Suppression of ACh-induced current (ACh current) was eliminated completely under the effects of 3–30 μM with depolarization of up to 80–100 mV at the membrane. Suppression of ACh current produced by membrane potential at negative levels is intensified with increasing doses of ACh. Findings would indicate that blockade of ionic channels opened by ACh is the only mechanism of TC action on nicotinic cholinoreceptors in rat sympathetic ganglia.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-9007
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ionic mechanisms of EPSP generation and depolarization induced by iontophoretic application of acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5-HT) — acetylcholine and serotonin potentials — were investigated in neurons of the isolated rabbit superior cervical ganglion by means of intracellular microelectrodes. The reversal potentials (Er) for EPSP and the ACh-potential were −14.4±1.6 and −16.5±1.2 mV respectively, and they were about the same for the 5-HT potential. In some neurons (about one-third) much more negative values for Er were obtained for EPSP and the ACh-potential by extrapolation, probably due to an increase in the resistance of their membrane during hyperpolarization. A decrease in the external sodium and potassium concentrations was shown to make Er for EPSP and the ACh-potential more negative, whereas an increase in the external potassium concentration made it more positive than in normal solution; a change in the external chloride concentration did not alter Er. It is suggested that the excitatory transmitter and exogenous ACh (and also, probably, 5-HT) share the same ionic mechanism of action of the membrane, which includes an increase in the permeability of the membrane to two ions — sodium and potassium — simultaneously.
    Type of Medium: Electronic Resource
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