IP3 receptor purified from liver plasma membrane is an (1,4,5)IP3 activated and (1,3,4,5)IP4 inhibited calcium permeable ion channel

doi:10.1016/0143-4160(95)90083-7

Cell Calcium

Volume 17, Issue 2, February 1995, Pages 141-153

https://doi.org/10.1016/0143-4160(95)90083-7 Get rights and content

Abstract

The IP₃ receptor is involved in Ca²⁺ mobilization from intracellular stores. Recently, we purified an inositol (1,4,5)-trisphosphate receptor from rat liver plasma membrane (LPM-IP₃R) [Schäfer R. Hell K. Fleischer S. (1993) Purification of an IP₃ receptor from liver plasma membrane. Biophys. J. 66, A146] . The purified LPM-IP₃ 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)IP₃] (1 μM) and inhibited by inositol (1,3,4,5)-tetrakisphosphate (IC₅₀ ∼1 μM) and by heparin (IC₅₀ ∼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)IP₃ is specific to the cis-side of the chamber, equivalent to the cytoplasmic face. The receptor is a Ca²⁺ permeable ion channel based on ion selectivity (Ca²⁺ > K⁺ > Na⁺ ⪢ Cl⁻). The LPM-IP₃ receptor was also permeable to Cs (Cs⁺ ≥ K⁺), similar to other intracellular Ca²⁺ release channels, i.e. the IP₃ receptor from brain and smooth muscle (IP₃R-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 Ca²⁺. The open probability of the (1,4,5)IP₃ activated channel activity displays a bell shaped response to cis Ca²⁺ ion concentration of our system. The LPM-IP₃ receptor differs from intracellular IP₃R-1 in that the Ca²⁺ and ATP concentration required for maximum activation is about 10 times higher as compared with IP₃R-1 from brain cerebellum and smooth muscle. We conclude that the LPM-IP₃ receptor is an (1,4,5)IP₃ activated Ca²⁺ permeable ion channel. The implication of our studies is that in liver, (1,4,5)IP₃ regulates Ca²⁺ influx via the plasma membrane.

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IP3 receptor purified from liver plasma membrane is an (1,4,5)IP3 activated and (1,3,4,5)IP4 inhibited calcium permeable ion channel

Abstract

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

Cell Calcium

J. Biol. Chem.

Cell Calcium

J. Biol. Chem.

Meth. Enzymol.

Biophys. J.

J. Theor. Biol.

Anal. Biochem.

Cell Calcium

Meth. Enzymol.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Meth. Enzymol.

Neuron

Biophys. J.

Biochemistry and biophysics of excitation-contraction coupling

Annu. Rev. Biophys. Biophys. Chem.

Expression of a ryanodine receptor-Ca2+ channel that is regulated by TGF-β

Science

Structure of a novel InSP3 receptor

EMBO J.

Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues

Neurobiology

IP₃ receptor purified from liver plasma membrane is an (1,4,5)IP₃ activated and (1,3,4,5)IP₄ inhibited calcium permeable ion channel

Expression of a ryanodine receptor-Ca²⁺ channel that is regulated by TGF-β

Structure of a novel InSP₃ receptor