The IP 3 receptor is involved in Ca 2 + mobilization from intracellular stores. Recently, we purified an inositol (1,4,5)-trisphosphate receptor from rat liver plasma membrane (LPM-IP 3 R) [Schafer R. Hell K. Fleischer S. (1993) Purification of an IP 3 receptor from liver plasma membrane. Biophys. J. 66, A146] . The purified LPM-IP 3 receptor was incorporated into vesicle derived planar bilayers and its channel properties characterized. The receptor displayed ion channel activity that was activated by inositol (1,4,5-trisphosphate [(1,4,5)IP 3 ] (1 μM) and inhibited by inositol (1,3,4,5)-tetrakisphosphate (IC 5 0 ~1 μM) and by heparin (IC 5 0 ~20 gm/ml). The channel displays a unitary conductance of 9 pS, and 13 pS in symmetrical 100 mM and 500 mM KCI, respectively, and in symmetrical 250 mM cesium methanesulfonate the slope conductance is 11 pS. Activation by (1,4,5)IP 3 is specific to the cis-side of the chamber, equivalent to the cytoplasmic face. The receptor is a Ca 2 + permeable ion channel based on ion selectivity (Ca 2 + > K + > Na + Cl - ). The LPM-IP 3 receptor was also permeable to Cs (Cs + >= K + ), similar to other intracellular Ca 2 + release channels, i.e. the IP 3 receptor from brain and smooth muscle (IP 3 R-1) and the ryanodine receptor from skeletal muscle (RyR-1) and heart (RyR-2). Channel activity is not voltage dependent (+/- 100 mV applied voltage). The channel is activated by ATP and Ca 2 + . The open probability of the (1,4,5)IP 3 activated channel activity displays a bell shaped response to cis Ca 2 + ion concentration of our system. The LPM-IP 3 receptor differs from intracellular IP 3 R-1 in that the Ca 2 + and ATP concentration required for maximum activation is about 10 times higher as compared with IP 3 R-1 from brain cerebellum and smooth muscle. We conclude that the LPM-IP 3 receptor is an (1,4,5)IP 3 activated Ca 2 + permeable ion channel. The implication of our studies is that in liver, (1,4,5)IP 3 regulates Ca 2 + influx via the plasma membrane.