MANY AGONISTS INDUCE QUANTAL CA2-BEHAVIOR IN MUSCLE RYANODINE RECEPTORS( RELEASE OR ADAPTIVE)

Ryanodine receptors have recently been shown to undergo an unusual kin d of inactivation process termed adaptation, which bears similarities to the transient calcium releases induced in other systems by successi ve incremental additions of inositol-1,4,5-trisphosphate. Such release s are sometimes termed ''quantal.'' In this study we report that many agonists induce similar behavior in muscle sarcoplasmic reticulum and that the responses depend not on the calcium pumps therein but rather on the ryanodine receptors; The chemical diversity of these agonists m akes it very unlikely that adaptation simply affects the sensitivity o f the receptor to agonists at any one binding site. More likely, this result indicates that adaptive behavior of ryanodine receptors results whenever the ryanodine receptor is activated and that this process af fects the action of most, if not all, agonists. Evidence is presented suggesting that the releases observed do not represent all-or-none rel eases from vesicle subpopulations (true quantal behavior) but rather s eem to involve partial release from more homogeneously sensitive store s, a process referred to here as adaptation or increment detection.