Luminal Ca2+ controls the activation of the inositol 1,4,5-trisphosphate receptor by cytosolic Ca2

• Published in: The Journal of biological chemistry Vol. 267; no. 32; pp. 22961 - 22966
• Main Authors: Missiaen, L, De Smedt, H, Droogmans, G, Casteels, R
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 15.11.1992
• Subjects: Animals; Aorta; Calcium - pharmacology; Calcium - physiology; Calcium Channels; Cell Line; Cell Membrane Permeability; Cytosol - metabolism; Egtazic Acid - pharmacology; Inositol 1,4,5-Trisphosphate - metabolism; Inositol 1,4,5-Trisphosphate - pharmacology; Inositol 1,4,5-Trisphosphate Receptors; Kinetics; Rats; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - metabolism; Receptors, Cytoplasmic and Nuclear
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)50041-7

Luminal Ca2+ controls the sensitivity of the intracellular Ca2+ stores to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). Ins(1,4,5)P3-induced Ca2+ release is also controlled by cytosolic Ca2+; low concentrations of Ca2+ stimulate the release. The aim of this work was to investigate whether luminal Ca2+ would affect the stimulation of the Ins(1,4,5)P3 receptor by cytosolic Ca2+ in permeabilized A7r5 smooth muscle cells. We also report that the Ins(1,4,5)P3 receptor in A7r5 cells is activated by low concentrations of cytosolic Ca2+. Cytoplasmic Ca2+ increases the Ins(1,4,5)P3 sensitivity without affecting the cooperativity. The increase in Ins(1,4,5)P3 sensitivity becomes relatively more pronounced when the Ca2+ content of the stores decreases. This modulatory effect of luminal Ca2+ on the responsiveness to cytosolic Ca2+ is an intrinsic property of the Ins(1,4,5)P3 receptor.