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Electrophysiological characterization of histamine receptor subtypes in mammalian heart preparations (1986)

Borchard, U. ; Hafner, D.

Springer

Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 294-302

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ISSN: 1432-1912

Keywords: H-receptor agonists ; Antihistamines ; Mammalian heart ; Action potentials ; Voltage clamp

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary Histamine-induced electrophysiological effects have been investigated in guinea-pig left atria, papillary muscles and rabbit AV-nodal preparations by means of intracellular recording of action potentials, slow responses in the presence of 27 mmol/l (K+)o and voltage clamp experiments. Differentiation of the H-receptor subtypes was performed by the use of the H2-selective agonists dimaprit and impromidine and the H1- and H2-selective antagonists dimetindene and cimetidine, respectively. The following results were obtained: 1. Histamine and the H2-agonists dimaprit and impromidine show similar actions on electrophysiological parameters of ventricular myocardium. Histamine at concentrations 〈1 μmol/l leads to a small increase in APD30 and APD90, but to a marked decrease at concentrations ≥ 1 μmol/l, whereas $$\dot V_{\max } $$ , resting potential and amplitude remain nearly unchanged. The effects on APD are completely blocked by cimetidine and not changed by dimetindene. Changes in action potential may be explained by an increase in slow inward current and outward currents as shown by voltage clamp experiments. 2. In left atria histamine increases APD30 and APD90, whereas there is only a minor increase in amplitude with no changes in $$\dot V_{\max } $$ and resting potential. These effects are completely reversed by the H1-antagonist dimetindene but not by cimetidine. IBMX decreases APD90 and does not potentiate the action of histamine. 3. $$\dot V_{\max } $$ of slow responses is increased in left atria by stimulation of H1-receptors and in papillary muscles by stimulation of H2-receptors. The results suggest that stimulation of atrial H1-receptors directly causes an increase in Ca-channel conductance. 4. Differentiation of the positive inotropic actions in left atria by means of TTX, diltiazem and vanadate suggests that histamine increases Ca-conductance but does not affect Na-dependent window current. 5. Histamine reduces AH-interval, increases $$\dot V_{\max } $$ of NH-cells and induces AV-arrhythmias at concentrations ≥ 1 μmol/l. The results indicate that these effects are due to stimulation of H2-receptors.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00508785

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Effects of the calcium entry blocker bepridil on repolarizing and pacemaker currents in sheep cardiac Purkinje fibres (1989)

Berger, F. ; Borchard, U. ; Hafner, D.

Springer

Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 638-646

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ISSN: 1432-1912

Keywords: Sheep Purkinje fibre ; Voltage clamp ; Ionic outward currents ; Calcium entry blocker ; Bepridil

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary (1) Effects of bepridil (0.3–100 μmol/l) on transmembrane currents which are active during the repolarization of the cardiac action potential were studied in sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique. Transmembrane currents were activated at a frequency of 0.03 Hz. (2) The initial inwardly rectifying current (i K1) was reduced by 1.8 μmol/l bepridil to 70% of the reference i K1-current in the absence of the drug. (3) An initial outward current, which is activated at positive membrane potentials (i inst) was depressed to 70% of reference by 14 μmol/l bepridil. (4) The time-dependent outward current (i K) was decreased by 1.8 μmol/l bepridil to 70% of its amplitude in the absence of bepridil. The biexponential time course of i K-current activation changed to be monoexponential with 100 μmol/l bepridil. The effect of bepridil on i K-current resulted in a shift of the activation curve of i K-current to more positive membrane potentials (10 μmol/l bepridil) and an additional decrease of driving force and/or conductance of the i K-channels with higher bepridil concentrations (100 μmol/l). (5) The transient outward current (i to) was completely blocked by 30 μmol/l bepridil. Inhibition to 70% of reference occurred with 1 μmol/l bepridil. The voltage-dependent inactivation of i to-current was affected by bepridil: the amplitude of the steady-state inactivation curve was reduced and i to-current was inactivated faster after application of bepridil. Bepridil caused no pronounced shift of the steady-state inactivation curve along the voltage axis. (6) The pacemaker current (i f) was slightly increased under the influence of low bepridil concentrations (0.3, 1 μmol/l) while it was reduced to 70% of reference by 100 μmol/l bepridil. (7) The blocking action of bepridil on outward currents in sheep cardiac Purkinje fibres will explain the action potential prolongation, which is observed in different mammalian cardiac tissues under the influence of bepridil.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00168656

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Monomeric methylmethacrylate (MMA) acts on the desheathed myelinated nerve and on the node of Ranvier (1977)

Böhling, H. G. ; Borchard, U. ; Drouin, H.

Springer

Archives of toxicology 38 (1977), S. 307-314

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ISSN: 1432-0738

Keywords: Methylmethacrylate (MMA) ; Desheathed sciatic nerve ; Sucrose gap method ; Node of Ranvier ; Voltage clamp

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Description / Table of Contents: Zusammenfassung Es wurde der Einfluß von monomerem Methylmethacrylat (MMA) auf das Ruhe- und Summenaktionspotential des isolierten entscheideten N. ischiadicus des Frosches (Saccharose-Trennwand-Methode) untersucht. Oberhalb von 10 mM trat eine dosisabhängige Abnahme des Summenaktionspotentials und eine Hyperpolarisation der Membran auf, die mit zunehmender MMA-Konzentration anstieg (4.1 mV±0.2 S.E.M. nach 50 mM MMA). Die durch niedrige [Ca2+]0 oder Veratrin hervorgerufene Depolarisation ließ sich durch MMA rückgängig machen. Die homologen Äthyl-, Allyl- und n-Butylester waren wirksamer als MMA, der Isobutylester weniger wirkungsvoll, während Na-Methacrylat und Methacrylsäureamid keinen Einfluß zeigten. Voltage clamp Experimente am isolierten Ranvierschen Schnürring zeigten, daß 50 mM MMA zu einer Abnahme der Na+- und K+-Ströme führten.

Notes: Abstract The influence of monomeric methylmethacrylate (MMA) on resting and compound action potential of the isolated desheathed sciatic nerve of the frog (sucrose gap method) was determined. Above 10 mM there was a dose-dependent decrease of the compound action potential and a hyperpolarization of the membrane which was augmented with increasing MMA concentrations (4.1 mV±0.2 S.E.M. after 50 mM MMA). The depolarization in low [Ca2+]0 solutions or with veratrine was reversed by MMA. The homologous ethyl, allyl and n-butyl esters were more effective than MMA, and the isobutyl ester less effective, whereas Na-methacrylate and methacrylamide showed no influence. Voltage clamp experiments on the node of Ranvier indicated that 50 mM MMA led to a decrease of the Na+ and K+ currents.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00352035

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