Calcium release mechanisms in smooth muscle.

Properties of the intracellular Ca store were studied using saponin-skinned fiber bundles of guinea pig smooth muscles using a fluorescent Ca indicator method. There exist two Ca release mechanisms in the Ca store: Ca-induced Ca release (CICR) and inositol 1,4,5-trisphosphate (IP3)-induced Ca release (IICR) mechanisms. The smooth muscle Ca store consists of two compartments: one (S alpha) has both CICR and IICR, and the other (S beta) has only IICR. The smooth muscle CICR is activated by greater than 1 microM Ca2+, has essentially the same properties with that in striated muscles, and is open-locked by ryanodine. After ryanodine treatment, therefore, the Ca uptake capacity of S alpha is selectively lost ('functional removal') with no effect on S beta. The IICR is Ca2(+)-dependent: Ca2+ enhances the IICR below 300 nM, but has also an inhibitory effect above this concentration. Therefore, Ca2+ acts on the IICR in a positive feedback manner when muscle tension is about to rise, making IP3 more effective, but this feedback is cut off as the tension approaches the maximum. ATP enhances the IICR as is the case in the CICR. 'Functional removal' of S alpha in intact bundles by ryanodine was used to estimate the role of Ca release in agonist-induced contractions. Ca release from the S alpha is important at least in the initial phase of contractions; and in the pulmonary artery, most of the activator Ca2+ originates from S alpha.