Distinct modes of inhibition by ruthenium red and ryanodine of calcium-induced calcium release in avian atrium.
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.
Vites
A M
AM
Department of Pharmacology, University of Connecticut Health Center, Farmington.
Pappano
A J
AJ
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002645:Chickens; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011343:Procaine / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D012430:Ruthenium Red; D012433:Ryanodine; D002110:Caffeine; D011343:Procaine; D002118:Calcium