1. Rapid ligand-regulated gating kinetics of single inositol 1,4,5-trisphosphate receptor Ca2+ release channels
- Author
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J. Kevin Foskett, King Pan Campion Loong, Don-On Daniel Mak, Marisabel Fernández-Mongil, Suman Datta, and John E. Pearson
- Subjects
Endoplasmic reticulum membrane ,Insecta ,Patch-Clamp Techniques ,Voltage-dependent calcium channel ,Scientific Report ,Cooperativity ,Biology ,Inositol trisphosphate receptor ,Ligands ,Biochemistry ,Cell biology ,Cell Line ,chemistry.chemical_compound ,chemistry ,Genetics ,Ligand-gated ion channel ,Animals ,Inositol 1,4,5-Trisphosphate Receptors ,Inositol ,Calcium ,Patch clamp ,Calcium Channels ,Signal transduction ,Molecular Biology ,Ion Channel Gating - Abstract
The ubiquitous inositol 1,4,5-trisphosphate receptor (InsP(3)R) intracellular Ca(2+) release channel is engaged by thousands of plasma membrane receptors to generate Ca(2+) signals in all cells. Understanding how complex Ca(2+) signals are generated has been hindered by a lack of information on the kinetic responses of the channel to its primary ligands, InsP(3) and Ca(2+), which activate and inhibit channel gating. Here, we describe the kinetic responses of single InsP(3)R channels in native endoplasmic reticulum membrane to rapid ligand concentration changes with millisecond resolution, using a new patch-clamp configuration. The kinetics of channel activation and deactivation showed novel Ca(2+) regulation and unexpected ligand cooperativity. The kinetics of Ca(2+)-mediated channel inhibition showed the single-channel bases for fundamental Ca(2+) release events and Ca(2+) release refractory periods. These results provide new insights into the channel regulatory mechanisms that contribute to complex spatial and temporal features of intracellular Ca(2+) signals.
- Published
- 2007