Fast release of calcium 45 induced by inositol 1 4 5 trisphosphate and calcium in the sarcoplasmic reticulum of rabbit skeletal muscle evidence for two types of calcium release channels

Valdivia, C.; Vaughan, D.; Potter, B.V.L.; Cornodo, R.

Biophysical Journal 61(2 Part 2): A24


ISSN/ISBN: 0006-3495
Accession: 007344347

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The kinetics of Ca2+ release induced by the second messenger D-myoinositol 1,4,5 trisphosphate (IP3), by the hydrolysis-resistant analogue D-myoinositol 1,4,5 trisphosphorothioate (IPS3), and by micromolar Ca2+ were resolved on a millisecond time scale in the junctional sarcoplasmic reticulum (SR) of rabbit skeletal muscle. The total Ca2+ mobilized by IP3 and IPS3 varied with concentration and with time of exposure. Approximately 5% of the 45Ca2+ passively loaded into the SR was released by 2 .mu.M IPS3 in 150 ms, 10% was released by 10 .mu.M IPS3 in 100 ms, and 20% was released by 50 .mu.M IPS3 in 20 ms. Released 45Ca2+ reached a limiting value of .apprx.30% of the original loading at a concentration of 10 .mu.M IP3 or 25-50 .mu.M IPS3. Ca2+-induced Ca2+ release (CICR) was studied by elevating the extravesicular Ca2+ while maintaining a constant 5-mM intravesicular 45Ca2+. An increase in extravesicular Ca2+ from 7 nM to 10 .mu.M resulted in a release of 55 .+-. 7% of the passively loaded 45Ca2+ in 150 ms. CICR was blocked by 5 mM Mg2+ or by 10 .mu.M ruthenium red, but was not blocked by heparin at concentrations as high as 2.5 mg/ml. In contrast, the release produced by IPS3 was not affected by Mg2+ or ruthenium red but was totally inhibited by heparin at concentrations of 2.5 mg/ml or lower. The release produced by 10 .mu.M Ca2+ plus 25 .mu.M IPS3 was similar to that produced by 10 .mu.M Ca2+ alone and suggested that IP3-sensitive channels were present in SR vesicles also containing ruthenium red-sensitive Ca2+ release channels. The junctional SR of rabbit skeletal muscle may thus have two types of intracellular Ca2+ releasing channels displaying fast activation kinetics, namely, IP3-sensitive and Ca2+-sensitive channels.