Biomaterial Database

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. 1995

M Mayrleitner, and R Schäfer, and S Fleischer

Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee, USA.

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 microM) and inhibited by inositol (1,3,4,5)-tetrakisphosphate (IC50 approximately 1 microM) and by heparin (IC50 approximately 20 micrograms/ml). The channel displays a unitary conductance of 9 pS, and 13 pS in symmetrical 100 mM and 500 mM KCl, 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+ > or = 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.

UI	MeSH Term	Description	Entries
D007295	Inositol Phosphates	Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.	Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D008051	Lipid Bilayers	Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.	Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D004553	Electric Conductivity	The ability of a substrate to allow the passage of ELECTRONS.	Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D006493	Heparin	A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.	Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia