The effects of inositol phosphates on Ca2+ uptake in cardiac junctional sarcoplasmic reticulum (JSR) vesicles was investigated. Inositol 1,3,4,5-tetrakisphosphate (IP4) selectively increased Ca2+ uptake 2.8 fold over basal levels whereas 1,3,4-IP3, 1,4,5-IP3 or 1,4-IP2 were without effect. Stimulation of Ca2+ uptake by IP4 was maximal within 15-60 sec at 30 degrees C and ATP-independent. Following incubation of JSR with ruthenium red, Ca2+ uptake in the presence or absence of IP4 was further enhanced 2.5 fold. Both basal and IP4-stimulated Ca2+ uptake were half-maximal and maximal in the presence of 60 nM and 180 nM Ca2+, respectively. These studies indicate that IP4 stimulates an ATP-independent Ca2+ uptake mechanism in cardiac JSR which may function to promote rapid Ca2+ loading.