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1.
Summary Membrane and action potentials of rat diaphragm fibres were measured in vitro as affected by quinidine, procaine amide, and N-propyl-ajmaline in concentrations of 10–5 to 10–4 g/ml.All three drugs had immediate effects on the action potential; the effects progressed the faster, the higher the concentration: the de- and repolarization were slowed, the duration increased, the overshoot decreased. Later (e.g., 1 h after application of 10–5 g/ml quinidine) the resting potential started to decrease and the fibres became inexcitable.Electrical threshold was increased and the refractory period was prolonged by all three drugs, most effectively by N-propyl-ajmaline, least by procaine amide. All drugs abolished myotonic symptoms produced by reduction of extracellular chloride.Quinidine and N-propyl-ajmaline (10–5 to 10–4 g/ml) produced a transitory increase of contraction force, on prolonged drug action the muscle went into contracture. Procaine amide always had a negative inotropic effect. All drugs increased contraction time.This work was supported by the Deutsche Forschungsgemeinschaft.  相似文献   

2.
Summary The influence of membrane potential on the effects of the enantiomers and the racemate of Bay K 8644 [1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluor-methylphenyl)-pyridine-5-carboxylate] on force of contraction and on action potentials were studied in guinea-pig papillary muscles in order to detect possible changes in the direction of drug action or in potency. Membrane potential was varied by changing the potassium concentration ([K+]o) in the bathing solution.At normal resting potential, (–)-Bay K 8644 enhanced force of contraction and prolonged the action potential duration measured at 50% of repolarization (APD) to the same extent as the racemate and with similar pD2 values. After membrane depolarization by raising ([K+]o) from 5.4 to 17.4 mmol/l, the (–)-enantiomer and the racemate prolonged the APD to a similar degree but enhanced force to a lesser extent. The maximum rate of depolarization of slow action potentials, V max, was increased at the highest concentrations (10–5 mol/l). The effects of (+)-Bay K 8644 were more complicated. At high concentrations (10–5 mol/l) it decreased force of contraction and APD, the pD2 values were one order of magnitude lower than for the (–)enantiomer and the racemate. A high concentration (+)-Bay K 8644 (10–5 mol/l) virtually abolished contractile activity at all membrane potentials, the extent of shortening in APD increased with membrane depolarization in elevated ([K+]o) V max, of slow action potentials was decreased. In normal bathing solution and with low concentrations of (+)-Bay K 8644(< 10–7 mol/l), the APD showed a small but significant prolongation which disappeared with membrane depolarization. No significant opposite effects in force of contraction were observed. There was no evidence for a potential-dependent shift in potency of drug action of either enantiomers or racemate.In papillary muscles potential-dependent opposite actions could be demonstrated for the effects of the inhibitory enantiomer on action potential duration. Corresponding changes in inotropic effects of DHPs are obscured by the intrinsic influence of depolarization on contractile activation. Send offprint requests to U. Ravens at the above address  相似文献   

3.
Summary Tachyphylaxis and susceptibility to pretreatment with reserpine demonstrate that tyramine increases contractility of the guinea-pig papillary muscle in concentrations up to 10–4 M by means of an indirect sympathomimetic effect.In higher concentrations (up to 3×10–3 M) tyramine causes an increase in force of contraction which is characterized by a slowing of relaxation of the isometric contraction curve. Pretreatment with reserpine reveals that this positive inotropic effect is composed of an indirect sympathomimetic and a direct post-synaptic effect; the latter is not subject to tachyphylaxis and produces by itself (at 3×10–3 M) an increase in force of contraction which amounts to about 50% of the maximum of the indirectly produced inotropic effect.The postsynaptically-induced positive inotropic effect of tyramine is not antagonized by propranolol (5×10–6 M). It is unlikely, therefore, that it is brought about by stimulation of adrenergic -receptors.The height of the isometric contraction curve in reserpine-pretreated muscles is increased by tyramine as a result of an increase in the rate of force development despite a marked concentration-dependent increase in relaxation time (t 2).The direct inotropic effect of tyramine is correlated with a prolongation of the duration of the action potential (AP) which amounts to 70% at 3×10–3 M. In addition to its influence on the duration of the AP, tyramine slows the rate of depolarization and decreases the membrane resting potential.  相似文献   

4.
Summary The positive inotropic effect of noradrenaline on the guinea-pig papillary muscle is potentiated in the presence of 1×10–5 M tyramine, the concentration of noradrenaline that is necessary to produce a half maximal increase in force of contraction being reduced to about one third. There is no alteration of the maximal inotropic effect since the concentration-effect curve of noradrenaline is simply shifted to the left.In the presence of 3×10–3 M tyramine, which by itself increases contractility by a dual mechanism (an indirect sympathomimetic and a direct postsynaptic one which is not induced by stimulation of adrenergic -receptors), noradrenaline (1×10–5 M) produces an additional inotropic effect leading to a force of contraction which surmounts the maximum of the normal concentration-effect curve of noradrenaline by about 30%.The supramaximal isometric contraction curve of the papillary muscle produced by the combined effects of 3×10–3 M tyramine and 1×10–5 M noradrenaline differs from the contraction curve in the presence of 1×10–5 M noradrenaline alone in having a steeper ascending slope and a slower relaxation phase. The mean velocity of force development (S 1) exceeds the maximum value of the normal concentration-effect curve of noradrenaline by about 50%. There is no increase in the maximum of the mean velocity of relaxation (S 2).The relaxation time of the supramaximal contraction curve as well as the duration of its action potential are the result of the opposing influences of the two substances, noradrenaline shortening and tyramine prolonging both action potential and relaxation time.  相似文献   

5.
Summary Lidocaine (3 · 10–5 and 10–4 M) and equimolar concentrations of brufacian dose-dependently reduced the depolarization velocity (dV/dtmax) and the force of contraction of guinea pig atria and papillary muscles. Repolarization time was increased in atria but reduced in papillary muscles. The maximum effects on action potential parameters were identical but developed with brufacain more slowly than with lidocaine.In papillary muscles lidocaine (3 · 10–5 M) prolonged the functional refractory period. No such effect but even a shortening was observed with brufacain. As brufacain reduced the duration of the action potential (AP) more than the functional refractory period, the relative refractory period (in percent of AP duration) was slightly prolonged. The half-time of the recovery of the Na+ system was increased three to five times the control value after lidocaine but only doubled after brufacain.Some of these results were presented at the 17th Spring Meeting of the German Pharmacological Society, March 23rd–26th, 1976.  相似文献   

6.
Summary Parameters of action and resting potentials of dog Purkinje and ventricular muscle fibers were studied after the administration of droperidol and fentanyl given separately and in combination (in a weight proportion 50:1 as in neuroleptanalgesia). Droperidol in all concentrations studied (10–6 M, 5×10–6 M, 10–5 M) moderately shortened action potential duration in electrically driven Purkinje fibers. Effective refractory period was also shortened but to a lesser degree than action potential duration. The drug was also able to diminish the automaticity in Purkinje fibers. It exerted nearly no effect on resting membrane potential, action potential amplitude and on maximum rate of depolarization. The latter was only slightly decreased by the highest concentration of the drug. Also conduction velocity in Purkinje fibers was not changed by the drug. Ventricular action potentials were not significantly influenced by droperidol. Fentanyl administered in concentrations 2.2×10–7 M and 1.1×10–6 M was devoid of any action on cardiac transmembrane potentials. The effects exerted by both drugs administered simultaneously were similar to the effects exerted by droperidol administered as a sole agent. The electrophysiological effects of droperidol on the isolated cardiac tissue are very similar to the action of lidocaine and diphenylhydantoin.This work was presented in the preliminary form at the Eighth Annual Meeting of the European Society for Clinical Investigation, April 25–27, 1974, Rotterdam  相似文献   

7.
Summary The mean membrane potential of smooth muscle cells of the rabbit main coronary artery was-60.3 mV and an evoked action potential could be recorded in response to acetylcholine (ACh). Ergonovine or 5-hydroxytryptamine (5-HT) slightly depolarized the membrane and methysergide, a relatively selective antagonist for the 5-HT receptor, had a slight inhibitory action on these depolarizations. 5-HT produced larger contractions than ergonovine, and the concentration-effect relationships obtained for both agents shifted to higher concentrations following pre-equilibration with methysergide. ACh (10–11 M) slightly hyperpolarized the membrane and relaxed the tissue, and high concentrations of ACh (>10–8 M) depolarized the membrane, increased the membrane resistance and produced a contraction. ACh but not ergonovine or 5-HT, produced a contraction in Ca-free EGTA-containing solution. Following a 60 min pre-equilibration with indomethacin, the ergonovine-induced contraction was markedly enhanced but the 5-HT-or ACh-induced contractions were not. Removal of the endothelium by rubbing the vascular lumen enhanced the ergonovine-or ACh-induced contractions, but not those to 5-HT.The results obtained can be summarized as follows: ergonovine probably accelerates Ca influx and thereby produces contraction in the rabbit main coronary artery. This contraction is due to activation of the 5-HT receptor as an agonist, but the ergonovine-induced contraction is attenuated due to activation of the endothelium from which inhibitory prostanoid substances may be released. Ergonovine, therefore, may produce greater contractions in coronary arteries with damaged endothelium than in intact tissues.  相似文献   

8.
The effects of okadaic acid (OA), a monocarboxylic acid produced by marine dinoflagellates belonging to the genera Dinophysis and Prorocentrum, and their interactions with theophylline and caffeine were studied on the rat-isolated uterus in a calcium-containing medium and a calcium-free medium in the presence of 10–3 M EGTA.Okadaic acid (5 × 10–6 to 5 × 10–5 M) induced a concentration-dependent contraction of the rat-isolated uterus corresponding, with 5 × 10–5M, to 142.3±6.1% (n = 7) of the contraction induced by oxytocin 10–6 M. The time to peak tension was inversely proportional to the maximum effect produced. The contraction was not sustained and was followed by a concentration-dependent decrease in tone. In a Ca2+-free medium containing 10–3 M EGTA the contractile effects of OA were significantly inhibited or reduced. A 30 min pretreatment with theophylline (3 × 10–3 M) or caffeine (2 × 10–2 M) significantly reduced, in a Ca2+-containing medium, the maximum contractile effect of OA 10–5 and/or 2 × 10–5 M and shortened the relative time to peak tension. In a Ca2+-free medium containing 10–3 M EGTA, only the second effect was observed. With a 1 min pretreatment and in a Ca2+-containing medium, theophylline 3 × 10–3 M and caffeine 10–2 M did not modify the maximum effect of OA 10–5 M but shortened the time to peak tension. The same concentrations of the xanthines potentiated the Emax of OA 5 × 10–6 M in the Ca2+-containing medium or in a Ca2+-free medium containing 10–3 M EGTA. Okadaic acid 10–6 M used as 30 min pretreatment versus OA 10–5 M and 2 × 10–5 M behaved like caffeine or theophylline.These results suggest that the OA-induced contraction of the rat uterine smooth muscle is partly effected by transmembrane calcium movements which can be inhibited in an O-Ca2+–10–3 M EGTA solution or by theophylline or caffeine. This contraction also involves mobilization of Ca2+ from an intracellular pool which is also xanthine-sensitive. The latter effect seems to be important in inducing the contractile effect. This study does not exclude the possibility of other mechanisms being involved in the contraction induced by OA. Correspondence to: M. L. Candenas at the above address in Burjassot-València  相似文献   

9.
Summary Sparteine at 10–5 to 10–4 g/ml increased the contraction time of rat diapharagm by a factor of 1.3, and amplitude by a factor of 2 to 3. The increase in force was transient, 15 min after drug application the amplitude began to fall, to reach 50% of the control within 85 min. The effects were reversible on washout. At 10–3 g/ml the depressant action was predominant, so that the muscle ceased to contract after 5 min. All these results can be explained by the effects of sparteine on the action potential: decrease of the rates of rise and fall led to a prolonged duration of the action potential, and a progressive decrease of the amplitude. These effects caused an increase of the refractory period by a factor of 2.5. For this reason sparteine was very effective in stabilizing the membrane of muscle fibres made myotonic by reduction of extracellular chloride.This work was supported by the Deutsche Forschungsgemeinschaft.  相似文献   

10.
Zusammenfassung Es wurde der Einfluß von Adrenalin auf mechanische Oscillationsphänomene isolierter Meerschweinchenpapillarmuskeln bei Temperaturen zwischen 19 und 25°C und bei verschiedenen Calciumkonzentrationen untersucht. Die isometrischen Kontraktionskurven wurden zusammen mit den intracellulär abgeleiteten Aktionspotentialen registriert.Bei niedriger Calciumkonzentration (0,4 mM und 140 mM Na+) verstärkt Adrenalin die bei einer Reizfrequenz 1 sec–1 während der Dauer der Depolarisation in der Erschlaffungsphase auftretende zweite Kontraktionswelle, die sich nun als eigener Kontraktionsgipfel neben dem ebenfalls vergrößerten ersten Kontraktionsgipfel abhebt.Verringerung der Reizfrequenz führt unter der Einwirkung von Adrenalin neben einer weiteren Verlängerung der Aktionspotentialdauer zur Ausbildung eines dritten Kontraktionsgipfels, der Papillarmuskel oscilliert auf erhöhtem Spannungsniveau solange die Membrandepolarisation andauert.Bei hoher Calciumkonzentration (9,6 mM und 140 mM Na+) bewirkt Adrenalin (3·10–7 bis 4,8·10–6 M) nach erfolgter Repolarisation der Membran das Auftreten von erregungsfreien Nachkontraktionen, wie es bei Erhöhung des Quotienten [Ca]/[Na]2 durch Verringerung der Natriumkonzentration oder unter dem Einfluß herzwirksamer Glykoside der Fall ist.Adrenalin (6·10–7 M) verkürzt die Aktionspotentialdauer bei 3,2 mM Ca und 20–23°C wie auch bei 9,6 mM Ca und 35°C um 12%. Bei 0,4 mM Ca++ verlängert Adrenalin in niedrigen Konzentrationen die AP-Dauer bei 35° und 20–23°C, während höhere Adrenalinkonzentrationen (6·10–7 bis 10–5 M) die AP-Dauer bei niedriger Temperatur auch geringgradig verkürzen können.
Summary The influence of epinephrine on oscillatory contraction phenomena of isolated guinea pig papillary muscles was studied in dependence on different calcium concentrations at temperatures between 19 and 25°C. The isometric contraction curves were recorded simultaniously with the intracellular action potentials.Epinephrine enhances the second contraction wave which appears at low calcium concentrations (0,4 mM) during the duration of the action potential at the stimulation frequency 1 sec–1.Lowering the stimulation frequency leads under the action of epinephrine to the appearance of a third contraction peak during the prolonged action potential.At high calcium concentration (9,6 mM) the action of epinephrine leads to the development of aftercontractions (new contraction waves after the complete repolarisation of the membrane) as it is the case due to a further increase of the quotient [Ca]/[Na]2 by lowering the sodium concentration or to the action of glycosides.Epinephrine shortens the duration of the action potential at higher calcium concentrations (3,2 mM at 20–23°C and 9,6 mM at 35°). At low calcium concentration (0.4 mM) epinephrine in low concentrations prolongs the action potential at 20–23°C and at 35°C; higher concentrations of epinephrine may shorten the AP duration somewhat at low temperatures.


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