Inositol 1,4,5-trisphosphate receptor isoforms show similar Ca2+release kinetics

Abstract

The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular Ca2+release channel which upon activation initiates many cellular functions. Multiple InsP3R subtypes are expressed in most cell types but the physiological significance of this heterogeneity is poorly understood. This study has directly compared the functional properties of the three different InsP3R isoforms by analyzing their InsP3-induced Ca2+release (IICR) properties in cell lines which predominantly express each isoform subtype. The InsP3-dependence of the amount or extent of IICR was InsP3R isoform-specific, with the type III isoform having the lowest affinity with respect to Ca2+release. The transient kinetics of IICR, measured using stopped-flow spectrofluorimetry, however, were similar for all three InsP3R isoforms. At maximal InsP3concentrations (20μM) the rate constants where between 0.8 and 1.0s−1for the fast phase and 0.25–0.45s−1for the slow phase. The concentration of InsP3required to induce half-maximal rates of Ca2+release (EC50) were also similar for the three isoforms (0.2–0.4μM for the fast phase and 0.75–0.95μM for the slow phase). These results indicate the InsP3R channel does not significantly differ functionally in terms of Ca2+release rates between isoforms. The temporal and spatial features of intracellular Ca2+signals are thus probably achieved through InsP3R isoform-specific regulation or localization rather than their intrinsic Ca2+efflux properties.