Effects of ryanodine on the properties of Ca2+ release from the sarcoplasmic reticulum in skinned skeletal muscle fibres of the frog.

1. We studied the effects of ryanodine on the functions of the sarcoplasmic reticulum (SR) in skinned muscle fibres from Xenopus laevis. 2. Ryanodine treatment decreased the Ca2+ uptake capacity of the SR in a fixed Ca2+ loading condition. The extent of the decrease in the SR Ca2+ uptake capacity was closely correlated with the activity of the Ca(2+)‐induced Ca2+ release (CICR) during the ryanodine treatment. This suggests, in agreement with the previous biochemical results, that ryanodine acts on the CICR channels when they are open. 3. The rate of Ca2+ leakage from the SR increased after ryanodine treatment. However, the leakage rate constants were independent of the degree of the loss of SR Ca2+ uptake capacity by the ryanodine treatment. This is inconsistent with the notion that the SR is a single uniform compartment and that the decline in the SR Ca2+ uptake capacity is a result of the increase in the Ca2+ leakage. 4. Partial recovery of the Ca2+ uptake capacity of the ryanodine‐treated SR was observed when Ca2+ loading was carried out in the presence of 10 mM procaine. This indicates that procaine partially blocks the open‐locked channels. 5. After Ca2+ loading in the presence of procaine, removal of procaine induced a rapid release of Ca2+ from the SR through the open‐locked channels. This rapid release was dependent both on the adenine nucleotide concentration and on the Ca2+ concentration. Thus, the ‘open‐locked’ CICR channels are still regulated by Ca2+ and adenine nucleotides.

[1]  G. Lamb,et al.  Control of calcium release and the effect of ryanodine in skinned muscle fibres of the toad. , 1990, The Journal of physiology.

[2]  H. Takeshima,et al.  Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor , 1989, Nature.

[3]  K. Horiuti,et al.  Mechanism of contracture on cooling of caffeine‐treated frog skeletal muscle fibres. , 1988, The Journal of physiology.

[4]  Harold P. Erickson,et al.  Purification and reconstitution of the calcium release channel from skeletal muscle , 1988, Nature.

[5]  K. Campbell,et al.  Purified ryanodine receptor from skeletal muscle sarcoplasmic reticulum is the Ca2+-permeable pore of the calcium release channel. , 1987, The Journal of biological chemistry.

[6]  É. Rousseau,et al.  Ryanodine modifies conductance and gating behavior of single Ca2+ release channel. , 1987, The American journal of physiology.

[7]  H. Erickson,et al.  Evidence for a junctional feet-ryanodine receptor complex from sarcoplasmic reticulum. , 1987, Biochemical and biophysical research communications.

[8]  J. Casida,et al.  Ca2+-activated ryanodine binding: mechanisms of sensitivity and intensity modulation by Mg2+, caffeine, and adenine nucleotides. , 1987, Molecular pharmacology.

[9]  S. Fleischer,et al.  Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. , 1987, The Journal of biological chemistry.

[10]  G. Meissner,et al.  Ryanodine activation and inhibition of the Ca2+ release channel of sarcoplasmic reticulum. , 1986, The Journal of biological chemistry.

[11]  K. Horiuti.  Some properties of the contractile system and sarcoplasmic reticulum of skinned slow fibres from Xenopus muscle. , 1986, The Journal of physiology.

[12]  S. Fleischer,et al.  Localization of Ca2+ release channels with ryanodine in junctional terminal cisternae of sarcoplasmic reticulum of fast skeletal muscle. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Hathaway,et al.  High molecular weight proteins in cardiac and skeletal muscle junctional sarcoplasmic reticulum vesicles bind calmodulin, are phosphorylated, and are degraded by Ca2+-activated protease. , 1984, The Journal of biological chemistry.

[14]  M. Endo,et al.  Calcium release from the sarcoplasmic reticulum. , 1977, Physiological reviews.

[15]  R. J. Podolsky,et al.  Calcium uptake and force development by skinned muscle fibres in EGTA buffered solutions , 1972, The Journal of physiology.

[16]  D. Jenden,et al.  The pharmacology of ryanodine. , 1969, Pharmacological reviews.

[17]  S. Ebashi.  Excitation-contraction coupling and the mechanism of muscle contraction. , 1991, Annual review of physiology.

[18]  M. Endo,et al.  Measurement of Ca2+ release in skinned fibers from skeletal muscle. , 1988, Methods in enzymology.

[19]  W. Chandler,et al.  A non‐linear voltage dependent charge movement in frog skeletal muscle. , 1976, The Journal of physiology.

[20]  M. Endo.  Conditions Required for Calcium-Induced Release of Calcium from the Sarcoplasmic Reticulum , 1975 .

[21]  M. Endo,et al.  Calcium-Induced Calcium Release and "Depolarization"-Induced Calcium Release: their Physiological Significance , 1975 .