Modulation of mammalian inositol 1,4,5-trisphosphate receptor isoforms by calcium: a role of calcium sensor region

¹ UT Southwestern Medical Center at Dallas

^* To whom correspondence should be addressed. E-mail: ilya.bezprozvanny{at}utsouthwestern.edu.

Submitted on July 14, 2004
Revised on August 23, 2004
Accepted on 29 October 2004

	Abstract

In the accompanying paper (Tu et al, 2004) we compared main functional properties of the 3 mammalian inositol 1,4,5-trisphosphate receptors (InsP3R) isoforms. In this paper we focused on modulation of mammalian InsP3R isoforms by cytosolic Ca2+. We found that: (1) when recorded in the presence of 2 mM InsP3 and 0.5 mM ATP all 3 mammalian InsP3R isoforms display bell-shaped Ca2+ dependence in physiological range of Ca2+ concentrations (pCa 8 - pCa 5); (2) in the same experimental conditions InsP3R3 is most sensitive to modulation by Ca2+ (peak at 107 nM Ca2+), followed by InsP3R2 (peak at 154 nM Ca2+), and then by InsP3R1 (peak at 257 nM Ca2+); (3) increase in ATP concentration to 5 mM had no significant effect of Ca2+-dependence of InsP3R1 and InsP3R2; (4) increase in ATP concentration to 5 mM converted Ca2+-dependence of InsP3R3 from "narrow" shape to "square" shape; (5) ATP-induced change in the shape of InsP3R3 Ca2+-dependence was mainly due to >200-fold reduction in the apparent affinity of Ca2+-inhibitory site; (6) the apparent Ca2+ affinity of Ca2+ sensor region (Cas) determined in biochemical experiments is equal to 0.23 mM Ca2+ for RT1-Cas, 0.16 mM Ca2+ for RT2-Cas, and 0.10 mM Ca2+ for RT3-Cas; (7) Ca2+ sensitivity of InsP3R1 and InsP3R3 isoforms recorded in the presence of 2 mM InsP3 and 0.5 mM ATP or 2 mM InsP3 and 5 mM ATP can be exchanged by swapping their Cas regions. Obtained results provide novel information about functional properties of mammalian InsP3R isoforms and support an importance of Ca2+ sensor region (Cas) in determining the sensitivity of InsP3R isoforms to modulation by Ca2+.

Key Words: calcium signaling, inositol (1,4,5)-trisphosphate receptor, planar lipid bilayers, single channels, structure-function

This article has been cited by other articles:

				X. Chen, T.-S. Tang, H. Tu, O. Nelson, M. Pook, R. Hammer, N. Nukina, and I. Bezprozvanny Deranged Calcium Signaling and Neurodegeneration in Spinocerebellar Ataxia Type 3 J. Neurosci., November 26, 2008; 28(48): 12713 - 12724. [Abstract] [Full Text] [PDF]

				D. Parthimos, R. E. Haddock, C. E. Hill, and T. M. Griffith Dynamics of A Three-Variable Nonlinear Model of Vasomotion: Comparison of Theory and Experiment Biophys. J., September 1, 2007; 93(5): 1534 - 1556. [Abstract] [Full Text] [PDF]

				H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]

				J. K. Foskett, C. White, K.-H. Cheung, and D.-O. D. Mak Inositol Trisphosphate Receptor Ca2+ Release Channels Physiol Rev, April 1, 2007; 87(2): 593 - 658. [Abstract] [Full Text] [PDF]

				I. Baran Gating Mechanisms of the Type-1 Inositol Trisphosphate Receptor Biophys. J., August 1, 2005; 89(2): 979 - 998. [Abstract] [Full Text] [PDF]

				S. Kim, T. Ahn, and C. Park The Pro335 -> Leu Polymorphism of Type 3 Inositol 1,4,5-Trisphosphate Receptor Found in Mouse Inbred Lines Results in Functional Change J. Biol. Chem., July 15, 2005; 280(28): 26024 - 26031. [Abstract] [Full Text] [PDF]