To more fully define differences between agents indicative of multiple sites of action, we studied changes in contractility and action potential (AP) configuration in cat ventricular myocytes produced by six cardiac glycosides (ouabain, ouabagenin, dihydroouabain, actodigin, digoxin, and resibufogenin). The effects of EO on the myocardial action potential and transient potassium efflux (Ito) were measured by patch clamping. Ouabain abolished both the p.d. In contrast to ouabain. In the presence of ouabain (5 × 10 −4 M ), the membrane potential depolarized to a constant level for 1‐4 hr, then hyperpolarized for 5‐7 hr after which it gradually depolarized again. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 ,uM ouabain. The negative inotropic effect of acetylcholine was reduced by treatment with ouabain.3. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 microM ouabain. At 10 nM ouabain, action potential duration is prolonged. To determine whether the responses of resting membrane potential (RMP) and hyperpolarization-activated current (IH) are altered by the application of ouabain, one of the Na+-K+ pump inhibitors, in neonatal rat small-diameter (<30microm) nodose ganglion (NG) neurons, we examined the effects of 1microM ouabain on those responses using perforated patch-clamp techniques. The potential would be above the resting state and can potentially lead to active depolarization. mV in 10 mV increments for 250 msec. At 10 nM ouabain, action potential duration is prolonged. six cardiac glycosides on action potential and contractile characteristics, and showed that digitoxin has a dose-related prolongation effect on action potential duration. Dihydro-ouabain or reduction of [K] o below 5.9 mM augment the positive inotropic effect of veratridine, while the interaction between veratridine and noradrenaline is additive. The calcium current was blocked by adding 0.1 mM CdCl 2 to Tyrode's solution. 6. Ouabain therefore potentiated the effect of membrane potential on calcium influx. The threshold for decrease in ak, increase in aeK, and de-crease in membrane potential is 1 ,uM, at which con-centration … At 10 nM ouabain, action potential duration is prolonged. Alpha iK was measured with single and double-barrel K-sensitive electrodes. Methods: 14 rabbits were divided into two groups at random, control group and THP group. Electrophysiological measurements demonstrated that moderate concentrations of glucagon exerted only a small effect in prolonging atrial and ventricular action potentials. a holding potential of -80 mV to voltage steps from -40 to +60Figure 1. The mucosal to serosal flux of Na+ and the serosal to mucosal flux of Cl‐ were significantly decreased in the presence of ouabain. The effects of ouabain ... the duration of both the calcium-dependent action potential and the afterhyperpolarization following the action potential was prolonged by ouabain (≥10nM). Effects of E-4031, KB-R7943 and ouabain on the rat pap-illary muscles Objective: To study the effect and mechanism of tetrahydropalmatine (THP) ouabain-induced on delayed after depolarization (DAD) and anti-triggered ventricular arrhythmia in in-vivo rabbit heart. Ouabain at low concentrations (1.5 x 10-8 M/L) decreased intracellular K to a new steady level which was reached after several hours. This effect was: (a) approximately the same over a range of external potassium concentrations from 0.3 to 5 m m, although the absolute effect of ouabain over this range of potassium was much different; (b) probably not due to different isoforms of pumps in cells grown in ouabain compared to untreated cells; (c) apparently not a consequence of internalisation of pump‐glycoside complexes. The systolic blood pressure (SBP) of 10 of the 12 rats in the EO group, designated as the EO-sensitive (OS) rats, began to increase from the fifth week of treatment and was significantly higher compared with that of the control group 6 weeks later (P 0.01). After atrial action potentials disappeared, oscillatory potentials were recorded from an S-A nodal cell. The effect on the transmembrane action potentials normally seen with ouabain (an acceleration of repolarization) was noted even in the face of a negative inotropic effect at low Ca ++ concentrations. Rosen et al. These effects could explain the negative inotropic action of high concentrations of glycosides, as well as the action potential changes observed by several investigators. A prestep of 30 msec to -40 mV was used to inac-tivate sodium currents. Adrenaline elevated the depressed plateau of the action potential from calf and sheep Purkinje fibres, but ouabain and glucagon were without effect. Ruch SR(1), Nishio M, Wasserstrom JA. Its value depended on drug concentration. Ouabain / w ɑː ˈ b ɑː ɪ n / or / ˈ w ɑː b eɪ n, ˈ w æ-/ (from Somali waabaayo, "arrow poison" through French ouabaïo) also known as g-strophanthin, is a plant derived toxic substance that was traditionally used as an arrow poison in eastern Africa for both hunting and warfare. tiple sites of action, we studied changes in contractility and action potential (AP) configuration in cat ventricular myocytes produced by six cardiac glycosides (ouabain, ouabagenin, di-hydroouabain, actodigin, digoxin, and resibufogenin). However, in aggregates pretreated with ouabain (2.5 microM), the [Ca2+]i increase was almost threefold greater with potassium than with lithium (P less than 0.007). Effects of ouabain on the PVs without spontaneous activity. This suggests that sodium/calcium exchange has little voltage dependence in this situation. 3. This review article focuses on the cardenolide ouabain and discusses its various in vitro and in vivo effects, its role as an endogenous compound, its mechanisms of action, and its potential use as a therapeutic agent; placing especial emphasis on our findings of ouabain as a pro-cystogenic agent in autosomal dominant polycystic kidney disease (ADPKD). (1973) studied the toxic effect of ouabain on electrocar-diogram and transmembrane action potential in isolated canine Purkinje fibers. Inclusion of 1×10 −3 M ouabain into the 1×10 −3 M Ethacrynic acid perilymph perfusate reduced the anoxia sensitive negative potential by 50 to 80% in the utricle and cochlea respectively. Figure I Effects of ouabain on the action potential recorded from an atrial cell (up to 22 min) and an S-A nodal cell (26. The inotropic effects of ouabain were retained even after pretreatment with saxitoxin (5 μmol/l) or changing the holding potential to −40 mV (to inactivate Na + current). E-4031 at 3.0 µmol/L potentiated the positive inotropic effect of ouabain and shortened T75% (Table 3, Figs.1 and 3). We have studied the effect of hypoxia and ouabain on the muscle resting potential (RP) of the cockroach Periplaneta americana L. The experiments were done in insects reared either in normoxic or hypoxic conditions and treated, or not treated, with The positive inotropic effect of 1.6 μM veratridine declines progressively when the contraction frequency is reduced below 0.5 Hz; rested-state contractions (at 0.004 Hz) are not increased by 1.6 μM veratridine. They also help to understand the arrhythmogenic effects of high concentrations of digitalis. Predict the effect of the poison ouabain which blocks Na+/K+ pumps, on the neuronal action potential. Action potential durations were significantly influenced by alterations in frequency of contraction. The effect of membrane potential on the manifestations of ouabain-induced alterations in the electrical activity of shortened sheep cardiac Purkinje fibres was studied by a microelectrode technique. (B) The superimposed tracings show the effects of ouabain (0.1, 1μM) on the AP configuration and contractile force. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 microM ouabain. It was recently discovered that ouabain, long thought to be exclusively a plant product, is actually synthesized by animals, and secreted from the adrenal cortex to regulate body osmosis and cellular concentrations of sodium. bain, action potential duration is prolonged. Transmembrane potential, isometric tension, and K 42 content of sheep or calf myocardial bundles were recorded simultaneously during periods up to 30 hours. and ISC of the histamine‐stimulated gastric mucosa. The stimulatory effect of DBcAMP on H+ secretion was still present after pretreatment with cimetidine or atropine. Ouabain at 0.5 µmol/L increased LVSP-LVEDP, +dp/ Table 1. Author information: (1)Department of Medicine, Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, IL 60611, USA. Effects of ouabain on rat systolic blood pressure. Effect of cardiac glycosides on action potential characteristics and contractility in cat ventricular myocytes: role of calcium overload. 31 and 33 min) of the atrium isolated from a rabbit (day 90). 10. AP short-ening was observed only with ouabain … 4. (A) The tracings show an example of ouabain (1μM) induced PV firing in a PV without spontaneous activity. The development of a phase 4 depolarization was noted. Ouabain at 0.5 µmol increased the developed tension of contraction in the rat papillary muscles. The image below represents its biosynthesis and … both norepinephrine and isoproterenol produced positive inotropic effects … The effect was reversible. The purpose of this study was to evaluate the effects of aging on the LA electrophysiological heterogeneity and ouabain-induced arrhythmogenicity. What do you think would happen to the neuronal action potential if the concentration of sodium ions in the extracellular fluid decreased significantly, to the point of reversing the gradient? In four experiments, alpha ik and contractile force were measured in the same muscle. The slow inward current and the maximum slow conductance also decreased under ouabain. The long‐term effects of ouabain on the membrane potential of the Anisodoris giant neurone (G cell) were examined in cells maintained for periods of up to 15 hr at 11–13° C. 2. b) The action potential causes a change in the proteins on the vesicle membranes such that the vesicle binds to the cell membrane and begins exocytosis c) The action potential triggers voltage-gated Ca2+ channels to open and the Ca2+ that flows in starts a cascade of protein reactions that allows exocytosis of the neurotransmitters Ouabain is a selective Na+/K+, -ATPase inhibitor, binds to α2 /α3 subunit with Ki of 41 nM/15 nM. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 microM ouabain. Ouabain (10(-6) g/ml) caused characteristic alterations in the tension-frequency relationship, enhancing the contractile tension at low but not high frequencies. A similar anoxia sensitive negative potential was not produced by the application of ouabain in either the utricle or cochlea even though both potentials were reduced to negative values. The level of membrane potential was modulated by passing intracellular polarizing current. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 microM ouabain. Because the main electrophysiologic action of an opioid such as morphine is thought to involve hyperpolarization of the neuronal membrane attributable to the opening of K + channels, one possibility is that the synergistic effect of ouabain with morphine on spinal antinociception might be via an effect on K + channels through its inhibition of Na +-K + pump. At 10 nM ouabain, action potential duration is prolonged. 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