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.

• Publication year

  1994

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1994-03-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0022-3565(25)38589-7PMID 7511166
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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