Calcium Mobilization Mechanisms in Smooth Muscle

Abstract

The role of intracellular calcium store in calcium mobilization in smooth muscle cells was examined using guinea pig taenia caeci, portal vein and pulmonary artery. By using saponin-skinned fiber bundles, two calcium release mechanisms, calcium-induced calcium release (CICR) and inositoltrisphosphate-induced calcium release (IICR), were found in the calcium store. Caffeine caused calcium release by enhancing CICR. In the absence of sensitizing drugs such as caffeine, CICR could only be evoked with levels of free calcium above 1 μM. Similar to CICR, IICR was accelerated by calcium ion and by adenine and related compounds, and inhibited by procaine. However, unlike CICR, the enhancing effect of calcium ion on IICR was apparent in the submicromolar range. The two calcium release mechanisms were distributed heterogeneously in the whole calcium store. A part of the store, called Sα, was with both CICR and IICR, but the remainder (Sβ) was only with IICR and not with CICR. This heterogeneity was confirmed by using ryanodine, which specifically acts on the CICR mechanism to fix the CICR channel in an open state. Thus, after ryanodine treatment, Sa no longer accumulated calcium but Sβ did. When intact smooth muscle cells were treated with ryanodine in the presence of caffeine, caffeine contractures as well as the initial phase of agonist-induced contractions were abolished, indicating the essential role of Sa in these contractions.