The mechanism of the increase of tonic tension produced by caffeine in sheep cardiac Purkinje fibres. 1985

D A Eisner, and M Valdeolmillos

The effects of caffeine were examined on contraction and membrane current in voltage-clamped sheep cardiac Purkinje fibres. The photoprotein aequorin was injected into several cells in order to measure the intracellular ionized Ca concentration [( Ca2+]i). When the Na-K pump was inhibited, depolarization produced a twitch followed by a tonic component of tension. Repolarization produced an after-contraction. These components of tension were accompanied by corresponding increases of aequorin light. Caffeine (10 mM) decreased both the twitch and the after-contraction while increasing the tonic component. The application of caffeine also produced a transient increase of aequorin light, both during depolarization and at rest, which was followed by a maintained decrease in all three components of the light signal. In particular, although caffeine decreased the rise of aequorin light during prolonged depolarization it increased the tonic tension. The possibility that the effects of caffeine on tonic tension could be due to suppression of spontaneous Ca oscillations was rejected for the following reasons. (i) Ryanodine (which also abolishes Ca oscillations) decreased the magnitude of the tonic tension. (ii) Caffeine still increased tonic tension when it was added to a fibre exposed to ryanodine (1-10 microM). In the presence of ryanodine it was possible to measure [Ca2+]i and tonic tension without interference from Ca oscillations. The increase of tonic tension produced by caffeine could not be accounted for by a rise of [Ca2+]i. The results showed that, at a given level of Ca, caffeine increased tension. The results show that a large part of the increase of tonic tension produced by caffeine is due to an increase of the Ca sensitivity of the contractile apparatus rather than to changes of [Ca2+]i. The consequence of this observation for the experimental use of caffeine is discussed.

UI MeSH Term Description Entries
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
D011690 Purkinje Fibers Modified cardiac muscle fibers composing the terminal portion of the heart conduction system. Purkinje Fiber,Fiber, Purkinje,Fibers, Purkinje
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
D006329 Heart Conduction System An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart. Conduction System, Heart,Conduction Systems, Heart,Heart Conduction Systems,System, Heart Conduction,Systems, Heart Conduction
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000331 Aequorin A photoprotein isolated from the bioluminescent jellyfish Aequorea. It emits visible light by an intramolecular reaction when a trace amount of calcium ion is added. The light-emitting moiety in the bioluminescence reaction is believed to be 2-amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine (AF-350). Aequorine
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
D012433 Ryanodine A methylpyrrole-carboxylate from RYANIA that disrupts the RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL to modify CALCIUM release from SARCOPLASMIC RETICULUM resulting in alteration of MUSCLE CONTRACTION. It was previously used in INSECTICIDES. It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM.
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli

Related Publications

D A Eisner, and M Valdeolmillos
March 1987, Naunyn-Schmiedeberg's archives of pharmacology,
D A Eisner, and M Valdeolmillos
February 1972, The Journal of physiology,
D A Eisner, and M Valdeolmillos
January 1990, Comparative biochemistry and physiology. A, Comparative physiology,
D A Eisner, and M Valdeolmillos
October 1989, Cardiovascular research,
Copied contents to your clipboard!