The positive inotropic effect of ouabain on atria and ventricle strips of cycloheximide-pretreated (20 mg/kg i.p. 3 hr before sacrifice) guinea-pigs and rats was significantly reduced or absent. Similar results were obtained when actinomycin (8 X 10(-6)M) was added to the perfusion medium of rat ventricle strips for 30 min before ouabain. These results suggest that either the synthesis of a short-lived protein is required for the inotropic effect of ouabain, or that at least part of ouabain's inotropic effect is due to the stimulated synthesis of some protein(s).
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FASEB J
September 2024
Research Division Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels.
View Article and Find Full Text PDFEur J Appl Physiol
March 2024
Exercise Biology, Department of Public Health, Aarhus University, Aarhus, Denmark.
This historical review traces key discoveries regarding K and Na ions in skeletal muscle at rest and with exercise, including contents and concentrations, Na,K-ATPase (NKA) and exercise effects on plasma [K] in humans. Following initial measures in 1896 of muscle contents in various species, including humans, electrical stimulation of animal muscle showed K loss and gains in Na, Cl and H0, then subsequently bidirectional muscle K and Na fluxes. After NKA discovery in 1957, methods were developed to quantify muscle NKA activity via rates of ATP hydrolysis, Na/K radioisotope fluxes, [H]-ouabain binding and phosphatase activity.
View Article and Find Full Text PDFCurr Issues Mol Biol
September 2023
Department of Physiology, Biophysics and Neurosciences, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico 07360, Mexico.
Ouabain, an organic compound with the ability to strengthen the contraction of the heart muscle, was originally derived from plants. It has been observed that certain mammalian species, including humans, naturally produce ouabain, leading to its classification as a new type of hormone. When ouabain binds to Na/K-ATPase, it elicits various physiological effects, although these effects are not well characterized.
View Article and Find Full Text PDFCells
April 2023
Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
Two α-isoforms of the Na,K-ATPase (α and α) are expressed in the cardiovascular system, and it is unclear which isoform is the preferential regulator of contractility. Mice heterozygous for the familial hemiplegic migraine type 2 (FHM2) associated mutation in the α-isoform (G301R; α mice) have decreased expression of cardiac α-isoform but elevated expression of the α-isoform. We aimed to investigate the contribution of the α-isoform function to the cardiac phenotype of α hearts.
View Article and Find Full Text PDFFront Physiol
September 2022
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Several local Ca events are characterized in smooth muscle cells. We have previously shown that an inhibitor of the Na,K-ATPase, ouabain induces spatially restricted intracellular Ca transients near the plasma membrane, and suggested the importance of this signaling for regulation of intercellular coupling and smooth muscle cell contraction. The mechanism behind these Na,K-ATPase-dependent "Ca flashes" remains to be elucidated.
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