Regulation of InsP3R by Ca2+ and Cytosolic Ca2+ Dynamics

  • Vladislav S. Markin
  • Ilya Bezprozvanny


Hormonal stimulation leads to the generation of second messenger inositol(1,4,5)-trisphosphate (InsP3) and release of calcium (Ca2+) from intracellular calcium stores due to activation of inositol(1,4,5)-trisphosphate receptor (InsP3R). InsP3-induced Ca2+ release is widely utilized by multiple cell types and constitutes one of the major steps in calcium signaling pathway. The activity of InsP3R receptor is under tight control in the cell and its most important regulatory mechanisms is the feedback effect exerted by cytosolic Ca2+. Modulation of the InsP3R by Ca2+ has been demonstrated in permeabilized cell preparations, using isolated microsomal vesicles and in planar lipid bilayer experiments with reconstituted InsP3R. These studies demonstrated the bell-shaped Ca2+ dependency of InsP3R activity, manifested within the effective physiological range of cytosolic Ca2+ concentrations. In the first part of this chapter we describe the initial discovery of InsP3R modulation by cytosolic Ca2+, the progress of our understanding of Ca2+ feedback on the InsP3R and some recent suggestions regarding the variability in Ca2+ regulation of different InsP3R isoforms. In the second part of the chapter we will relate the InsP3R modulation by cytosolic Ca2+ to the complex spatiotemporal behaviour of Ca2+ signaling in cells, manifested as cytosolic Ca2+ waves and oscillations.


Wave Propagation Xenopus Oocyte Calcium Wave Generation Zone Inositol Trisphosphate 
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© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Vladislav S. Markin
    • 1
  • Ilya Bezprozvanny
    • 2
  1. 1.Department of Anesthesiology and Pain ManagementUniversity of Texas, Southwestern Medical Center at DallasDallasUSA
  2. 2.Department of PhysiologyUniversity of Texas, Southwestern Medical Center at DallasDallasUSA

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