Interactions between inositol 1,4,5-trisphosphate receptors and ryanodine receptors in smooth muscle: one store or two?

Abstract

This short review proposes a system of simplified functional models describing possible interactions between Ca 2+-release channels associated with IP 3Rs and RyRs in smooth muscle, and considers each of these models in the light of the available experimental evidence. Complete separation of IP 3R- and RyR-gated stores seems to be unusual. Where both receptors release Ca 2+ from a common pool, simple interactions can occur since changes in the activation of one receptor type affects the availability of Ca 2+ for release through the other. Alterations in [Ca 2+] within the sarcoplasmic reticulum can also affect the open probability of the release channels, and not just the Ca 2+-flux through the channels when open, e.g., Ca 2+-release through tonically active IP 3Rs appears to limit SR Ca 2+-content in some myocytes, and this modulates RyR activity, as indicated by changes in Ca 2+-spark frequency. There is also evidence that intracellular release channels may co-operate, leading to positive feedback during activation. In particular, agonist-dependent activation of IP 3Rs can promote activation of RyRs, amplifying and shaping the resulting Ca 2+-signal. While there is little direct evidence as to the mechanism responsible for this interaction, some form of Ca 2+-induced Ca 2+-release in response to local increases in [Ca 2+] c seems likely.