Faculty Collaboration Database

Rapid activation and partial inactivation of inositol trisphosphate receptors by inositol trisphosphate. Biochemistry 1998 Aug 18;37(33):11524-33

Date

08/26/1998

Pubmed ID

9708988

DOI

10.1021/bi980808k

Scopus ID

2-s2.0-0032544178 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

During superfusion of permeabilized hepatocytes, submaximal concentrations of inositol 1,4,5-trisphosphate (InsP3) evoked quantal Ca2+ mobilization: a rapid acceleration in the rate of 45Ca2+ release abruptly followed by a biphasic decline to the basal rate before the InsP3-sensitive stores had fully emptied. During the fast component of the decay, the Ca2+ permeability of the stores fell rapidly by 40% (t1/2 = 250 ms) to a state indistinguishable from that evoked by preincubation with InsP3 under conditions that prevented Ca2+ mobilization. This change was accompanied by a decrease in the InsP3 dissociation rate: the response declined more quickly when InsP3 was removed during the initial stages of a response than later. We suggest that InsP3 directly causes its receptor to rapidly switch (t1/2 = 250 ms) between a low-affinity (Kd approximately 1 microM) active, and a higher-affinity (Kd approximately 100 nM) less active, conformation, and that this transition underlies the fast component of the decaying phase of Ca2+ release. Ca2+ continues to leak through the unchanging less active state of the receptor until those stores that responded initially are completely empty, accounting for the slow phase of the response. The requirements for activation of InsP3 receptors are more stringent (InsP3 and then Ca2+ binding) than those for partial inactivation (InsP3 binding); rapid inactivation is therefore likely to determine whether the cytosolic [Ca2+] reaches the threshold for regenerative Ca2+ signals.

Author List

Marchant JS, Taylor CW

Author

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Calcium Channels
Calcium Radioisotopes
Cations, Divalent
Cell Membrane Permeability
Inositol 1,4,5-Trisphosphate
Inositol 1,4,5-Trisphosphate Receptors
Kinetics
Liver
Male
Models, Chemical
Protein Binding
Protein Conformation
Rats
Rats, Wistar
Receptors, Cytoplasmic and Nuclear