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  • 1
    Electronic Resource
    Electronic Resource
    Activation of membrane outward currents by human low density lipoprotein in mouse peritoneal macrophages (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 207-212 
    Details
    ISSN: 1432-1912
    Keywords: Macrophage ; Voltage-clamp ; Ionic current ; Low density lipoprotein ; Acetylated low density lipoprotein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to search for electrophysiological effects of human lipoproteins on membrane currents in mouse peritoneal macrophages which had been cultured for 5 to 20 days. Whole-cell currents were recorded by using a voltage-clamp technique. Low density lipoprotein (LDL, 100 μg/ml) increased a slowly activating nonspecific cation current (iso) in the positive potential range to 244 ± 23% of the reference (test potential + 55 mV, n = 13, P 〈 0.005). Augmentation of current resulted out of a negative shift of the activation curve along the voltage axis (−22 mV) and an increase of maximally available current. Furthermore, LDL increased a rapidly activating outward current (ifo) at test potentials positive to the potassium equilibrium potential. At +55 mV ifo-amplitude increasedto 165 ± 14% ofreference (n = 16, P 〈 0.005). LDL-induced effects on ifo-current could be mimicked by application of the calcium ionophore A 23187 (1 μmol/l) which led to an increase of ifo-current to 161 ± 25% of the reference (test potential + 55 mV, n = 11, P 〈 0.005). Acetylated-LDL (100 μg/ml, 5–15 min) produced no significant effect on the membrane currents under investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00164800
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  • 2
    Electronic Resource
    Electronic Resource
    Activation of a potassium outward current by zymosan and opsonized zymosan in mouse peritoneal macrophages (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 594-601 
    Details
    ISSN: 1432-1912
    Keywords: Macrophage ; Voltage-clamp ; Potassium current ; Zymosan ; Platelet activating factor ; Calcium ionophore A 23187
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of zymosan and human serum opsonized zymosan on membrane currents of adherent mouse peritoneal macrophages which had been cultured for 5 to 20 days were investigated with the whole-cell voltage-clamp technique. Both stimuli activated an outward current. The outward current activation was transient and lasted about 5 min. In solutions with 10 or 50 mmol/l extracellular potassium concentration the activation of an outwardly directed current occurred at test potentials positive to the respective potassium equilibrium potential. This particle-induced current resembled a calciu-mactivated potassium current which could be activated with the calcium ionophore A 23187 and with platelet activating factor. The order of maximal responses (test potential +55 mV, amplitude given as percentage of the respective control) was: 0.1 μmol/l platelet activating factor (222±36%,n=8,P〈0.01) 〉 1 μmol/l A 23187 (190±24%,n=11,P〈0.01) 〉900 μg/ml opsonized zymosan (134±7%,n=22,P〈0.01) 〉900 μg/ml zymosan (116±5%,n = 21,P〈0.01) The lower efficiency of zymosan as compared to opsonized zymosan is explained in part by a lower percentage of responding cells which was 48% for zymosan and 73% for opsonized zymosan. Macrophages which were pretreated with particles showed a greater reactivity to calcium as compared to untreated cells. Elevation of extracellular calcium from 0.9 to 4.5 mmol/l activated the outward current to 145±12% (n = 11,P〈 0.01) after preincubation with opsonized zymosan and to 144±21% (n = 12,P〈 0.01) under the influence of zymosan while in untreated cells current increase by elevation of extracellular calcium was not significant (120±10%,n = 9, n.s.).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01258465
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  • 3
    Electronic Resource
    Electronic Resource
    Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use-dependently in sheep cardiac Purkinje fibres (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 64-72 
    Details
    ISSN: 1432-1912
    Keywords: Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibition of the pacemaker current (i f) in sheep cardiac Purkinje fibres by ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride] is lost use-dependently. This disinhibition of i f was investigated by using the two-microelectrode voltage-clamp technique. The pulse protocol consisted of a rest period (holding potential of about -50 mV, 1–10 μmol/l ZD 7288) followed by a train of test pulses (potential negative to -100 mV, stimulation frequency 0.05 Hz). At the beginning of the first test pulse there was an immediate reduction of i f but inhibition was lost during continued stimulation. Activation of i f is sigmoidal and the early delay in current activation was prolonged from 33 ms (no ZD 7288) to 424 ms (10 μmol/l ZD 7288). Therefore hardly any disinhibition occurred during short test pulses (0.5 s). During longer test pulses (5 s, -120 mV, 10 μmol/l) disinhibition developed with a time constant of about 2 s. The inhibition of i f by ZD 7288 was lost voltage-dependently. With 10 μmol/l ZD 7288 the half-maximal disinhibition occurred at -92 mV and the slope factor of the disinhibition/voltage curve (Boltzmann relation) was 4.8 mV. The voltage-dependent disinhibition could be abolished largely by extracellular application of protease (0.5 mg/ml, 7 min). After prior disinhibition, reinhibition at the holding potential (about -50 mV) followed a bi-exponential time course indicating that inhibition may be produced by a fast (τ=0.7 min) and a slow component (τ=20–30 min). Increasing ZD 7288 concentration from 1 to 10 μmol/l accelerated reinhibition, mainly by an increase of the amplitude (A) of the fast component. The ratio A fast/A sIow was 0.399 at 1 μmol/l and 2.65 at 10 μmol/1 ZD 7288. The reinhibition of i f was unchanged by shifting the holding potential from -50 mV to -20 mV Trials to wash out the effects of 10 μmol/l ZD 7288 gave two results. The inhibition of i f was slightly reversed after a wash-out of 1.5 h with drug-free solution. A second effect of the drug, the fast reinhibition, could be completely removed by washout. In summary i f is inhibited by ZD 7288 at membrane potentials at which the virtual i f gate is closed. Disinhibition occurs during long-lasting hyperpolarization but will hardly be operative in unclamped fibres under physiological conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168917
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of the bradycardic agent ZD 7288 on membrane voltage and pacemaker current in sheep cardiac Purkinje fibres (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 677-684 
    Details
    ISSN: 1432-1912
    Keywords: Sheep cardiac Purkinje fibre ; Pacemaker current ; Action potential ; Bradycardic agent ; ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The bradycardic mechanism of ZD 7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride) was investigated in sheep cardiac Purkinje fibres. The pacemaker if-current measured with the two-microelectrode voltage-clamp technique, as well as the diastolic depolarization rate and the frequency of spontaneously active fibres were evaluated. ZD 7288 did inhibit if-current. The if-amplitude recorded with a 0.8s-lasting test pulse from about −50 mV to −100 mV was reduced to 50% of control at 0.85 μmol/l and to 5% of control at 10 μmol/l. The threshold potential of if-activation was unaffected at a concentration of 1 μmol/l ZD 7288. The time constant of if-activation at different test potentials was not changed by 1 μmol/l ZD 7288. The drug was equally effective during if-activation with a 0.5 s-lasting test pulse applied at 0.05 Hz or 0.5 Hz. During long lasting (5 s) hyperpolarizing test pulses (−120 mV) the inhibition of if-current was removed. In constantly stimulated Purkinje fibres (0.5 Hz) the slope of the early diastolic depolarization was decreased by ZD 7288. The half-maximal effect occurred at 0.92 μmol/l. There was strong correlation over the concentration range of 0.01 to 10 μmol/l ZD 7288 between the decrease of the slope of early diastolic depolarization and inhibition of if-amplitude recorded with 0.8s-lasting test pulses to −100 mV. The correlation coefficient was r = 0.97. These results will explain the decrease in frequency of spontaneously active (about 0.6 Hz) Purkinje fibres. At 0.3 μmol/l ZD 7288 spontaneous activity had stopped in 8 of 11 preparations. Complete recovery of drug-induced effects on the frequency was gained after 3 h of wash-out with drug-free solution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169374
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