Biomaterial Database

Caffeine contracture in guinea-pig ventricular muscle and the effect of extracellular sodium ions. 1988

T Kitazawa

Department of Pharmacology, Juntendo University School of Medicine, Tokyo, Japan.

1. The mechanisms underlying the virtual absence of caffeine contracture in guinea-pig heart in a Na+-rich external solution were reinvestigated in small (50-120 microns thick) bundles of intact and skinned papillary muscle fibres. 2. In Na+-free solution, the peak tension of 30 mM-caffeine contracture corresponded to the maximum tension of the skinned fibres, and was independent of changes in [Ca2+]o and [K+]o. In the presence of external Na+, the peak tension, which was at most several per cent of the maximum, was affected by [Ca2+]o, [Na+]o and [K+]o, and enhanced by Mn2+ and Ni2+. 3. In the absence of Ca2+, replacement of Na+ with K+ allowed caffeine to evoke a large contracture, showing that there was sufficient calcium stored in the cells under Na+-rich conditions. After treatment with 30 mM-caffeine in the Na+-rich, Ca2+-free solution, and upon replacement of all Na+ with Li+, caffeine was still able to produce a large contracture, which was dependent upon Ca2+ pre-loading of the cells before the first caffeine treatment and upon the subsequent duration in the Na+-free solution. 4. Replacement of Li+ with Na+ during the contracture led to rapid relaxation which was delayed by an increase in [Ca2+]o, depolarization by K+, and addition of La3+ and Mn2+. After Na+-induced complete relaxation in the absence of Ca2+, upon removal of the drugs and Na+, subsequent application of caffeine to the cells evoked a large contracture without Ca2+ reloading. 5. In the skinned fibres, 30 mM-caffeine increased the Ca2+ sensitivity of the contractile system and depressed the maximum tension. An increase in Na+ from 8.4 to 58.4 mM altered neither Ca2+ sensitivity nor the rate of tension development in the absence or presence of caffeine. 6. Increase in Na+ affected neither the rate nor the amount of Ca2+ uptake by the sarcoplasmic reticulum (SR) in the absence or presence of caffeine. Increasing Na+ slightly inhibited the caffeine-induced Ca2+ release from the SR, but more than 10 mM-caffeine produced SR Ca2+ depletion. 7. In the presence of a strong Ca2+ buffer, the steady level of Ca2+ uptake by the SR with 1 mM-caffeine was equal to the amount of Ca2+ remaining in the SR just after the application of caffeine, indicating that Ca2+ release was not inactivated.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007537	Isometric Contraction	Muscular contractions characterized by increase in tension without change in length.	Contraction, Isometric,Contractions, Isometric,Isometric Contractions
D008094	Lithium	An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.	Lithium-7,Lithium 7
D008345	Manganese	A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
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
D009532	Nickel	A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D002110	Caffeine	A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.	1,3,7-Trimethylxanthine,Caffedrine,Coffeinum N,Coffeinum Purrum,Dexitac,Durvitan,No Doz,Percoffedrinol N,Percutaféine,Quick-Pep,Vivarin,Quick Pep,QuickPep
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
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
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