Distinct modes of inhibition by ruthenium red and ryanodine of calcium-induced calcium release in avian atrium. 1994

A M Vites, and A J Pappano
Department of Pharmacology, University of Connecticut Health Center, Farmington.

We studied the properties of calcium-induced calcium release (CICR) and its regulation by inhibitors (caffeine, ryanodine, ruthenium red and procaine) in a multicellular atrial preparation that lacks T-tubules. CICR was elicited by application of brief (2-3 sec) calcium pulses (pCa 6.0-6.5). The transient contractions induced by these brief pulses were used to monitor the release of calcium from the sarcoplasmic reticulum in saponin-permeabilized chick atrial fibers. Prolonged (3-10 sec) calcium pulses produced contractions with a phasic CICR-mediated component followed by a tonic component due to direct activation of the myofilaments by calcium. Ryanodine (1 microM) suppressed the phasic but not the tonic contraction. CICR-mediated contractions are suppressed not only by ryanodine (IC50 = 23 nM), but also by ruthenium red (270 nM), procaine (8.1 mM) and millimolar caffeine. Ryanodine inhibits contractions mediated by CICR in a use-dependent manner, due to a strong requirement to act on the activated state of the calcium release channels. However, the blocking action of ryanodine does not require the presence of elevated myoplasmic calcium. A transient contraction occurs upon removal of procaine, which we attribute to unblocking of calcium release channels. Our previous studies of Ins(1,4,5)P3- and caffeine-induced calcium release together with the present work with CICR allow us to propose a model of SR calcium release mechanisms in avian atrial muscle in which corbular sarcoplasmic reticulum may participate.

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
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
D011343 Procaine A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). Anuject,Geriocaine,Gerokit,Hewedolor-Procain,Lophakomp-Procain N,Novocain,Novocaine,Procain Braun,Procain Jenapharm,Procain Rödler,Procain Steigerwald,Procain curasan,Procaina Serra,Procaine Hydrochloride,Pröcaine chlorhydrate Lavoisier,Röwo Procain,procain-loges,Hydrochloride, Procaine
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
D002645 Chickens Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA. Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006325 Heart Atria The chambers of the heart, to which the BLOOD returns from the circulation. Heart Atrium,Left Atrium,Right Atrium,Atria, Heart,Atrium, Heart,Atrium, Left,Atrium, Right
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
D012430 Ruthenium Red An inorganic dye used in microscopy for differential staining and as a diagnostic reagent. In research this compound is used to study changes in cytoplasmic concentrations of calcium. Ruthenium red inhibits calcium transport through membrane channels. Ammoniated Ruthenium Oxychloride,Oxychloride, Ammoniated Ruthenium,Red, Ruthenium,Ruthenium Oxychloride, Ammoniated

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