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  • Macrophage  (2)
  • (±)-Sotalol  (1)
  • (−)-noradrenaline  (1)
  • Acetylated low density lipoprotein  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 696-704 
    ISSN: 1432-1912
    Keywords: Sheep Purkinje fibre ; Outward currents ; Pacemaker current ; (+)-Sotalol ; (±)-Sotalol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was aimed to differentiate the action of (+)- and (±)-sotalol (10–1000 μmol/l) on membrane currents which are active during the repolarization of cardiac action potentials Effects where studied in shortened sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique Action potentials were activated at a frequency of 0.25 Hz and membrane currents at 0.03 Hz or 0.05 Hz in most experiments. Out of the currents investigated the transient outward current (ito) reacted most sensitively to (+)- and (±)-sotalol. Ito-amplitude was decreased on the average to 77% of reference at 10 μmol/l and to 53% at 1000 μmol/l (+)- or (±)-sotalol. The maximally available ito-current was decreased but the voltage-dependent control of inactivation was left nearly unchanged. The initial inwardly rectifying current (iKi), which propels the last repolarization phase of the action potential and controls resting potential to a large extent was reduced on the average to 93% of reference at 10 μmol/l and to 62% at 1000 μmol/l (+)- or (±)-sotalol. Time-dependent (delayed) outward current (iK) was on the average not affected by (+)- or (±)-sotalol up to 100 μmol/l and was decreased to 84% of reference current under the influence of 1000 μmol/l. An initial outward current, which is activated at positive membrane potentials (iinst) was not clearly affected by (+)- or (±)-sotalol at concentrations up to 1000 μmol/l Pacemaker current (if) was not influenced by the drugs up to 100 μmol/l. Only at 1000 μmol/l was the amount of available if-current decreased to 79% of reference. (The potential-dependent control of activation was not affected) Time constants of time-dependent currents ito, iK and if did not change in concentrations up to 1000 μmol/l of the drug. Action potential duration increased at (+)- or (±)-sotalol concentrations ≥ 10 μmol/l and maximal prolongation was achieved at concentrations of 100–300 μmol/l Resting potential remained nearly unchanged at these concentrations, but the membranes depolarized at 1000 μmol/l. According to our data action potential prolongation in sheep Purkinje fibres under the influence of (+)- and (±)-sotalol correlates to the drug-induced block to ito-current and inwardly rectifying iK1-current.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 594-601 
    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
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 207-212 
    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
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  • 4
    ISSN: 1435-1803
    Keywords: Sheep cardiac Purkinje fibers ; action potentials ; automaticity ; β1-β2- ; adrenoceptors-(−) ; isoproterenol ; (−)-noradrenaline ; procaterol ; bisoprolol ; ICI 118,551
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The electrophysiological effects mediated by β1- and β2- in spontaneously active sheep cardiac Purkinje fibers were investigated using the non-selective agonist (−)-isoproterenol (IPN) and the selective agonists (−)-noradrenaline (β1) and procaterol (β2) in the absence and presence of the selective antagonists bisoprolol (β1) and ICI 118,551 (β2). IPN (0.01 μmol/l) increased the spontaneous rate by 54% and the slope of diastolic depolarization by 68% of the respective control values. Further, IPN increased the action potential duration at −20 mV (APD −20 mV) from 96 to 154 ms, reduced the APD −70 mV by 17% and the duration of the diastole by 39% and slightly hyperpolarized the maximum diastolic potential. These effects were partially inhibited by ICI 118,551 (0.03 μmol/l), diminished by bisoprolol (0.1 μmol/l) and almost completely blocked by the combination of both antagonists. Concentration response curves of IPN were influenced by the selective antagonists as follows: ICI 118,551 (0.03 μmol/l) shifted the curves to the right by 0.2–0.4 log units and increased the slope factor. Bisoprolol (0.1 μmol/l) induced a greater shift to the right by 1.1–1.5 log units. Combination of bisoprolol with ICI 118,551 shifted the curves to the right by 1.5–1.7 log units. Noradrenaline (0.3 μmol/l) elicited similar actions as IPN. Bisoprolol (0.1 μmol/l) shifted the concentration response curves of noradrenaline to the right by 1.1–1.9 log units. Actions of procaterol (0.1 μmol/l) were weak, attained only 15–35% of the maximal effects of IPN and could be blocked by ICI 118,551 (0.03 μmol/l). These results show that the increase of pacemaker activity induced by catecholamines in sheep cardiac Purkinje fibers is predominantly mediated by stimulation of β1. However, contribution of β2 mediated effects could be demonstrated.
    Type of Medium: Electronic Resource
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