Inositol 1,4,5-trisphosphate receptor isoforms show similar Ca super(2+) release kinetics

The inositol 1,4,5-trisphosphate receptor (InsP sub(3)R) is an intracellular Ca super(2+) release channel which upon activation initiates many cellular functions. Multiple InsP sub(3)R 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 InsP sub(3)R isoforms by analyzing their InsP sub(3)-induced Ca super(2+) release (IICR) properties in cell lines which predominantly express each isoform subtype. The InsP sub(3)-dependence of the amount or extent of IICR was InsP sub(3)R isoform-specific, with the type III isoform having the lowest affinity with respect to Ca super(2+) release. The transient kinetics of IICR, measured using stopped-flow spectrofluorimetry, however, were similar for all three InsP sub(3)R isoforms. At maximal InsP sub(3) concentrations (20 mu M) the rate constants where between 0.8 and 1.0/s for the fast phase and 0.25-0.45/s for the slow phase. The concentration of InsP sub(3) required to induce half-maximal rates of Ca super(2+) release (EC sub(50)) were also similar for the three isoforms (0.2-0.4 mu M for the fast phase and 0.75-0.95 mu M for the slow phase). These results indicate the InsP sub(3)R channel does not significantly differ functionally in terms of Ca super(2+) release rates between isoforms. The temporal and spatial features of intracellular Ca super(2+) signals are thus probably achieved through InsP sub(3)R isoform-specific regulation or localization rather than their intrinsic Ca super(2+) efflux properties.