Ca2+ influx evoked by inositol‐3,4,5,6‐tetrakisphosphate in ras‐transformed NIH/3T3 fibroblasts

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Abstract
Infusion of inositol‐3,4,5,6‐tetrakisphosphate (Ins(3,4,5,6)P4) from the patch pipette into the cytoplasm, produced a biphasic intracellular free Ca2+ concentration ([Ca2+]i) increase in ras‐transformed NIH/3T3 (DT) cells. The Ins(3,4,5,6)P4‐induced increase in DT cells depended upon extracellular Ca2+ and was enhanced by membrane hyperpolarization. Identical [Ca2+]i increases were observed with intracellular application of inositol‐1,3,4,5‐tetrakisphosphate (Ins(1,3,4,5)P4) and inositol‐1,3,4,6‐tetrakisphosphate but not with inositol‐1,2,4,5‐tetrakisphosphate, inositol‐1,4,5‐trisphosphate or inositol‐1,3,4,5,6‐pentakisphosphate. Stimulation of DT cells with bradykinin increased the levels of Ins(3,4,5,6)P4 and Ins(1,3,4,5)P4. These results suggest that Ins(3,4,5,6)P4 may serve as a second messenger for continuous Ca2+ influx along with other tetrakisphosphates downstream from bradykinin receptors in DT cells.