Sodium load and high affinity ouabain binding in rat and guinea‐pig cardiac tissue

Herzig, Stefan; Mohr, Klaus

doi:10.1111/j.1476-5381.1985.tb16150.x

Cited by 13 publications

(3 citation statements)

References 15 publications

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“…Since dihydroouabain exhibited a higher potency in increasing aka and force of contraction in atrial than in ventricular myocardium, a high affinity isozyme of Na+,K+-ATPase could have prevailed in this type of tissue. On the other hand, the higher level of aka in atrial cells could have enhanced the turnover rate of the Na+ pump and thus increased the apparent affinity of Na'.K+-ATPase for the cardioactive steroid (Herzig & Mohr, 1985;Stimers, Lobaugh, Liu, Shigeto & Lieberman, 1990). Our measurement of Na+, K+-ATPase activity in preparations from guinea-pig ventricles and atria showed that the inhibitory potency of dihydroouabain on Na+,K+-ATPase was identical in both tissues (Fig.…”

Section: Discussionmentioning

confidence: 68%

Intracellular sodium activity and its regulation in guinea‐pig atrial myocardium.

Wang

Schmied

Ebner

et al. 1993

The Journal of Physiology

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SUMMARY1. Intracellular Na' activity (aIa) and membrane resting potential were studied in quiescent guinea-pig atrial and papillary muscles by means of Na'-sensitive and conventional microelectrodes. The effects of the cardioactive steroid dihydroouabain (DH11) on aia, force of contraction and sarcolemmal Na', K+-ATPase activity were also investigated.2. In thirty atria and twenty-two papillary muscles, a'a amounted to 8-0 + 0 2 and 4 7 +0 3 mm, respectively (means±+S.E.M.). When both tissues were from the same animal, with the same ion-sensitive microelectrode mean a'a values of 79 + 02 and 541 + 0-5 mm (P < 0 0 1) were obtained from eight atrial and eight papillary muscles, respectively.3. Membrane resting potentials (Em) were significantly (P < 0-001) more negative in the papillary muscles (-83 5 + 0 7 mV; n = 8) than in the atrium (-7841 + 0 5 mV; n = 8). Deviation of Em from EK (determined by K+-sensitive microelectrodes) was 30 + ±0)2 mV in ventricular (P < 0 05) and 641 + 0 3 mV in atrial preparations (/' < 0 05).4. Inhibition of the Na+ pump by DHO increased aia of the atrium within 10 min by 06+01 (n = 7). 13+01 (n = 5) and 32+02 mm (n = 5) at 5,10 and 30jCtM, respectively. In the papillary muscle, 10 yUM DHO was without effect while a'a rose by 1-0+0-1 (n = 5) and 2-9+02 mm (n = 6) at 30 and 120 /aM DHO.5. Consistent with the a'a measurements, the potency of DHO to increase force of the isometric contraction was three times higher in atrium than in papillary muscle (stimulation frequency 0 2 Hz).6. Hydrolytic activity of sarcolemmal Na+,K+-ATPase isolated from atria amounted to only one third of that detected in ventricles (0-07 +001, n = 6, versus 0-2+0±-01 /mol phosphate released min-(g tissue)-', n = 5). The inhibitory potencies of DHO on sarcolemmal Na+,K+-ATPase preparations were found to be identical in the enzymes from either tissue.

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Section: Discussionmentioning

confidence: 68%

Intracellular sodium activity and its regulation in guinea‐pig atrial myocardium.

Wang

Schmied

Ebner

et al. 1993

The Journal of Physiology

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“…Inhibition of the ENaC activates the endothelial nitric oxide synthase (eNOS) via phosphorylation and increases the production of NO [31]. In cardiac muscle, an increased sodium load has been shown to activate the Na + /K + -ATPase [17]. In this context, the level of endogenous ouabain, which blocks the Na + /K + -ATPase is increased in patients with hypertension [6,33].…”

Section: Introductionmentioning

confidence: 99%

Firewall function of the endothelial glycocalyx in the regulation of sodium homeostasis

Korte

Wiesinger

Straeter

et al. 2011

Pflugers Arch - Eur J Physiol

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Plasma sodium, slightly above normal and in presence of aldosterone, stiffens vascular endothelium and reduces nitric oxide release with the consequence of endothelial dysfunction. This process is mediated by epithelial sodium channels (ENaC) and, most likely, the endothelial Na(+)/K(+)-ATPase. Both, ENaC and Na(+)/K(+)-ATPase, are located in the plasma membrane of endothelial cells and embedded in the endothelial glycocalyx (eGC). This negatively charged biopolymer is directly exposed to the blood stream and selectively buffers sodium ions. We hypothesize that the glycocalyx could interfere with endothelial sodium transport when extracellular sodium varies in the physiological range. Therefore, we modeled the endothelial cell as a pump-leak system measuring changes of intracellular sodium in cultured human endothelial cells. Experiments were performed under low/high extracellular sodium conditions before and after enzymatic eGC removal, and with inhibition of Na(+)/K(+)-ATPase and ENaC, respectively. Three major observations were made: (1) eGC removal by heparinase treatment facilitates sodium to enter/exit the endothelial cells. (2) The direction of net sodium movement across the endothelial plasma membrane depends on the concentration of extracellular sodium which regulates both the Na(+)/K(+)-ATPase and ENaC activity. (3) Removal of eGC and inhibition of sodium transport modify the electrical resistance of endothelial cells. We conclude that the eGC serves as a potential "firewall" preventing uncontrolled access of sodium to the pump-leak system of the endothelial cell. After eGC removal, sodium access to the system is facilitated. Thus the pump-leak system could be regulated by ambient sodium and control vascular permeability in pathophysiological conditions.

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“…A possible reason for this difference is the higher intracellular Na + concentration present during whole-cell recording. A high c i Na is known to increase the affinity of the Na + /K + pump to cardiac steroids (Herzig and Mohr 1985;Stimers et al 1990;Bielen et al 1992).…”

Section: The Estimated K′ D Valuesmentioning

confidence: 99%

Na+/K+ pump inhibition and positive inotropic effect of digitoxigenin and some C-22-substituted derivatives in sheep cardiac preparations

Erlenkamp

Gretzer

Zillikens

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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Affinity labeling might be used to localize the binding site(s) of the lactone ring of cardioactive steroids on the Na+/K+-ATPase. The aim of the experiments described below was to identify C-22-substituted derivatives of digitoxigenin suitable for this purpose. The positive inotropic effect of digitoxigenin, 22-benzoyloxy-digitoxigenin, 22-acetoxy-digitoxigenin, 22-allyl-digitoxigenin, and 22-hydroxy-digitoxigenin was studied in sheep cardiac Purkinje fibres. In addition, the inhibition of the Na+/K+ pump by these drugs was investigated by means of simultaneous measurements of membrane current and intracellular Na+ concentration in voltage-clamped Purkinje fibres and by means of whole-cell recording in isolated sheep Purkinje cells. The experiments were performed at 5.4 mM K+ and 30 to 33 degrees C. All compounds exerted a reversible positive inotropic effect. The concentrations required for the half maximal effect (EC50 value) amounted to approximately 5 x 10(-7) M digitoxigenin, 22-acetoxy-digitoxigenin or 22-hydroxy-digitoxigenin. The EC50 values for 22-benzoyloxy-digitoxigenin and 22-allyl-digitoxigenin were estimated to be 1.3 x 10(-6) M and 1.1 x 10(-5) M, respectively. From measurements on voltage-clamped Purkinje fibres the concentrations required for half maximal Na+/K+ pump inhibition (K'D value) were calculated to be approximately 10(-6) M for digitoxigenin, 22-acetoxy-digitoxigenin or 22-hydroxy-digitoxigenin. The K'D value for 22-benzoyloxy-digitoxigenin was 10 times larger. The K'D value for 22-allyl-digitoxigenin was even larger and amounted to approximately 4 x 10(-5) M. The K'D values of the drugs derived from whole-cell recording on single Purkinje cells tended to be smaller by a factor 2 to 8. Measurements of drug binding and unbinding revealed that the apparent association rate constant of 22-benzoyloxy-digitoxigenin (approximately 9 x 10(2) s(-1) M[-1]) was smaller than the association rate constant of digitoxigenin (approximately 2 x 10(4) s(-1) M[-1]), whereas the apparent dissociation rate constants of both compounds were similar (approximately 4 x 10(-3) s[-1]). Compared to digitoxigenin 22-allyl-digitoxigenin displayed a lower association rate constant (approximately 3 x 10(3) s(-1) M[-1]) and a larger dissociation rate constant (approximately 8 x 10(-2) M[-1]). The structure-activity relationships of the drugs are discussed. We conclude that esters derived from 22-hydroxy-digitoxigenin might be suitable to localize the binding site(s) of the lactone moiety on the Na+/K+ pump by affinity labeling.

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Sodium load and high affinity ouabain binding in rat and guinea‐pig cardiac tissue

Cited by 13 publications

References 15 publications

Intracellular sodium activity and its regulation in guinea‐pig atrial myocardium.

Intracellular sodium activity and its regulation in guinea‐pig atrial myocardium.

Firewall function of the endothelial glycocalyx in the regulation of sodium homeostasis

Na+/K+ pump inhibition and positive inotropic effect of digitoxigenin and some C-22-substituted derivatives in sheep cardiac preparations

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