Bibliothek

X
feed icon rss

Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
Filter
  • Voltage-clamp  (5)
  • Sheep cardiac Purkinje fibre  (2)
  • transient outward current  (2)
  • 1
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Sheep cardiac Purkinje fibre ; Pacemaker current ; Action potential ; Bradycardic agent ; ZD 7288
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00169374
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 2
    Digitale Medien
    Digitale Medien
    Different inhibition patterns of tedisamil for fast and slowly inactivating transient outward current in rat ventricular myocytes (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 291-298 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Key words Rat ventricular myocyte ; Voltage-clamp ; Transient outward current ; Action potential ; Tedisamil
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Tedisamil has been described as a selective inhibitor of a fast inactivating transient outward current (ito,f) in rat ventricular myocytes. Because recent reports demonstrated the existence of a second slowly inactivating transient component (ito,s) we investigated ito,s and differentiated the effects of tedisamil on both transient outward current components and their influence on action potential duration. Standard electrophysiological techniques were used for whole cell recordings at 24–26° C from enzymatically isolated myocytes. Inhibition of ito,f by tedisamil was the result of an acceleration of inactivation at positive test potentials with a concentration for halfmaximal inhibition (EC50) of 4–7 μmol/l, which is confirmatory to reports from other investigators. Our new results show that ito,s is more sensitive to tedisamil with an EC50 of 0.5 μmol/l. Furthermore the pattern of ito,s inhibition is different compared with ito,f, because inactivation of ito,s is not accelerated by tedisamil. Instead the amplitude of the steady state inactivation curve of ito,s is attenuated which indicates a reduction of maximally available current. Ito,s was evaluated by three different methods as time-dependently inactivating current (7.5 s test pulse duration), voltage-dependently inactivated current and tedisamil-sensitive current. All approaches yield similar inactivation curves. The potential for halfmaximal inactivation of ito,s lies about 35 mV more negative than that for ito,f and the slope factor (K = –23 mV) is different to that of ito,f (K = –3 mV). Effectiveness of tedisamil-induced modulation of ito,f and ito,s on action potential repolarization was tested. Action potentials stimulated at 0.5 Hz were not prolonged by 1 μmol/l tedisamil (dominant ito,s block) at a repolarization level of 0 mV but prolonged to about 120% of control at –70 mV. This indicates that ito,f was sufficient to guarantee a regular early repolarization whereas decrease of ito,s delayed the final repolarization. In conclusion, the observation that tedisamil inhibits ito,f and ito,s differently supports the hypothesis that the two ito-components are related to two different channel populations expressed in rat ventricular myocytes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00005170
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 3
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00168917
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 4
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Key words Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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 slow was 0.399 at 1 μmol/l and 2.65 at 10 μmol/l 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 wash-out. 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00168917
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 5
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Macrophage ; Voltage-clamp ; Potassium current ; Zymosan ; Platelet activating factor ; Calcium ionophore A 23187
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01258465
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 6
    Digitale Medien
    Digitale Medien
    A slowly inactivating transient outward current in rat ventricular myocytes (1993)
    Springer
    Pflügers Archiv 425 (1993), S. 184-186 
    Details
    ISSN: 1432-2013
    Schlagwort(e): voltage clamp ; transient outward current ; cardiac myocytes ; tetrodotoxin ; cadmium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In rat ventricular myocytes we found two components of transient outward current, which could be discriminated time- and voltage-dependently. Besides the well known fastly inactivating transient outward current (ito,f, τ=35±8ms, n=4) we investigated properties of a slowly inactivating transient outward current (ito,s, τ=1.7±0.4s, n=4). Because of the slow inactivation process of ito,s tail currents were observed at −25mV. The inactivation curve of ito,f was characterized by a half-inactivation voltage of −58.4±1.4mV and a slope factor of 5.6±0.5mV (n=4). The inactivation curves of ito,s and tail currents were nearly identical but significantly different from the ito,f-curve. Half-inactivation voltages of ito,s and tail currents were −87.5±6mV and −89.1±5mV (n=4), respectively. Slope factors were 10.3±2.9mV and 9.8 ±1.7mV (n=4). The activation gate of ito,s was half-maximally opened at −11.5±2.6mV, and the slope factor was −10.6±1.7mV (n=3). ito,s tail current reversed its direction at −62±3.2mV (n=5). This indicates, that ito,s- current flow is carried mainly by potassium ions. Ito,s- current was not abolished by Tetrodotoxin (TTX) and Cd.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00374522
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 7
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Macrophage ; Voltage-clamp ; Ionic current ; Low density lipoprotein ; Acetylated low density lipoprotein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00164800
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 8
    Digitale Medien
    Digitale Medien
    Modulation of action potential duration by inhibition of the transient outward current in sheep cardiac Purkinje fibers (1995)
    Springer
    Basic research in cardiology 90 (1995), S. 185-191 
    Details
    ISSN: 1435-1803
    Schlagwort(e): Sheep Purkinje fiber ; voltage-clamp ; action potential duration ; transient outward current ; 4-aminopyridine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In sheep cardiac Purkinje fibers concentration-dependent inhibition of transient outward current (ito) by 4-aminopyridine (4-AP, 3-1000 μmol/l) was recorded with the two-microelectrode voltage-clamp technique, and correlated effects on action potential duration measured at — 70 mV (APD-70) were investigatigated. Half-maximal inhibition of ito-amplitude occurred at 15 μmol/l 4-AP. The drug exhibited no major effect on voltage-dependent control of inactivation but reduced the maximally available ito-current. At different activation frequencies (0.05 Hz, 0.25 Hz, 1 Hz) an equal amount of ito-current, measured as percentage of the respective control, was inhibited by 4-AP. The APD-70 was on the average increased by 4-AP (3–500 μmol/l) in a concentration-dependont manner up to 151 % of control. The drug-induced prolongation, measured as percentage of the respective control, was independent of stimulation frequency (0.05 Hz, 0.25 Hz, 1 Hz). Prolongation of APD-70 was on the average more pronounced for short action potentials (APD-70〈150 ms: 169 % of reference) than for longer ones (APD-70 150–300 ms: prolongation to 117 % of reference; 500 μmol/l 4-AP; 0.25 Hz stimulation rate). Few long control signals (APD-70 〉300 ms) were shortened by 4-AP. These results indicate that inhibition of ito-current by appropriate drugs will result in a reduction of inhomogeneity of action potential duration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00805661
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie hier...