Biomaterial Database

Reverse Na+/Ca2+ exchange contributes to glutamate-induced intracellular Ca2+ concentration increases in cultured rat forebrain neurons. 1998

K R Hoyt, and S R Arden, and E Aizenman, and I J Reynolds

Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.

Activation of ionotropic glutamate receptors causes increases in intracellular Ca2+ concentration ([Ca2+]i) and intracellular Na+ concentration in neurons. It has been suggested that reversal of the plasma membrane Na+/Ca2+ exchanger (NCE) may account in part for the rise in [Ca2+]i. Recently, KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) was reported to selectively inhibit the reverse mode of the NCE in non-neuronal cells. We investigated the effects of KB-R7943 on glutamate-stimulated increases in [Ca2+]i. In cultured rat forebrain neurons loaded with indo-1 acetoxymethyl ester, KB-R7943 inhibited the reverse mode of NCE (IC50 = 0.7 microM). When tested against kainate- (100 microM), N-methyl-D-aspartate- (30 microM), glutamate- (3 microM), or KCl- (50 mM) induced [Ca2+]i transients (15 sec, in the presence of Na+ and Ca2+), KB-R7943 inhibited these transients with IC50 values of 6. 6, 8.2, 5.2, and 2.9 microM, respectively. [Ca2+]i increases caused by a higher concentration of glutamate (100 microM) also were inhibited by KB-R7943 (10 microM). However, KB-R7943 had no effect on peak [Ca2+]i changes caused by prolonged application of glutamate and did not inhibit glutamate-induced neuronal injury. KB-R7943 did not inhibit N-methyl-D-aspartate- or kainate-induced whole-cell currents, nor did it substantially inhibit voltage-sensitive Ca2+ currents, excluding a direct inhibition of these ion channels. These results suggest that reverse NCE contributes to the immediate rise in [Ca2+]i resulting from glutamate receptor activation. However, reverse NCE becomes less important as the stimulus time is increased, and Ca2+ entry by this route is not critical for the expression of excitotoxic injury.

UI	MeSH Term	Description	Entries
D007424	Intracellular Fluid	The fluid inside CELLS.	Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D007608	Kainic Acid	(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.	Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
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
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D013890	Thiourea	A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.
D016202	N-Methylaspartate	An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).	N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,N Methylaspartate
D016548	Prosencephalon	The anterior of the three primitive cerebral vesicles of the embryonic brain arising from the NEURAL TUBE. It subdivides to form DIENCEPHALON and TELENCEPHALON. (Stedmans Medical Dictionary, 27th ed)	Forebrain,Forebrains