Calcium and the mechanism of action of digitalis. 1984

F Orrego

A critical review is made of the mechanism by which digitalis increases the force of contraction of heart muscle. First, it is concluded that the initial step is always an inhibition of the sodium pump, and that the postulated stimulation of the pump by low digitalis concentrations is, possibly, not a real phenomenon. Secondly, the major theories that try to explain the inotropic effect of digitalis are analyzed, and it is tentatively concluded that the effect occurs because Na increases close to the inner side of the plasma membrane, and this decreases Ca efflux through the Na-Ca "exchange" mechanism. An internal Ca store, probably the sarcoplasmic reticulum, that competes with the plasma membrane for Ca, is then able to capture and, subsequently release, a larger fraction of the Ca mobilized during each transient. It is also concluded that the digitalis-induced larger Ca transients can be entirely explained because of a greater Ca "injection" into the cytoplasm during each beat, and not because of changes in resting pCa. A comprehensive model is presented that seems to explain in some detail both the inotropic and the toxic effect of digitalis.

UI MeSH Term Description Entries
D007473 Ion Channels Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS. Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D008929 Mitochondria, Heart The mitochondria of the myocardium. Heart Mitochondria,Myocardial Mitochondria,Mitochondrion, Heart,Heart Mitochondrion,Mitochondria, Myocardial
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002451 Cell Compartmentation A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc. Cell Compartmentations,Compartmentation, Cell,Compartmentations, Cell
D003593 Cytoplasm The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990) Protoplasm,Cytoplasms,Protoplasms
D004071 Digitalis Glycosides Glycosides from plants of the genus DIGITALIS. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all CARDIAC GLYCOSIDES, but here is restricted to those related to Digitalis. Glycosides, Digitalis
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23

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