Acute ethanol alters calcium signals elicited by glutamate receptor agonists and K+ depolarization in cultured cerebellar Purkinje neurons. 1997

D L Gruol, and K L Parsons, and N DiJulio
Department of Neuropharmacology and Alcohol Research Center, Research Institute of Scripps Clinic, La Jolla, CA 92037, USA.

The effect of acute ethanol on Ca2+ signals evoked by ionotropic (iGluR) and metabotropic (mGluR) glutamate receptor (GluR) activation and K+ depolarization was examined in cultured rat cerebellar Purkinje neurons to assess the ethanol sensitivity of these Ca2+ signaling pathways. Mature Purkinje neurons approximately 3 weeks in vitro were studied. iGluRs were activated by (RS)-alpha-amino-3-hydroxyl-5 methyl-4-isoxazolepropionic acid (AMPA; 1 and 5 microM) and domoate (5 microM). mGluRs were activated by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD; 300 microM) and (R,S)-3,5-dihydroxyphenylglycine (DHPG; 200 microM). These agents and K+ (150 mM) were applied from micropipettes by brief (1 s) microperfusion pulses. Ca2+ levels were monitored at 2-3 s intervals during pre- and post-stimulus periods using microscopic digital imaging and the Ca2+ sensitive dye fura-2. iGluR and mGluR agonists and K+ produced abrupt increases in intracellular Ca2+ that slowly recovered to baseline resting levels. Acute exposure to ethanol at 33 mM (150 mg%) and 66 mM (300 mg%) significantly reduced the amplitude of the Ca2+ signals to iGluR agonists and K+ with little or no effect on Ca2+ signals to mGluR agonists. In contrast, acute ethanol at 10 mM (45 mg%) had no effect on the Ca2+ signals to the iGluR agonist AMPA but significantly enhanced the Ca2+ signals to the mGluR agonist DHPG. These results show that ethanol modulates Ca2+ signaling linked to GluR activation in a receptor subtype specific manner, and suggest that Ca2+ signaling pathways linked to GluR activation and membrane depolarization may be important mechanisms by which ethanol alters the transduction of excitatory synaptic signals at glutamatergic synapses and thereby affects intercellular and intracellular communication in the CNS.

UI MeSH Term Description Entries
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
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
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011689 Purkinje Cells The output neurons of the cerebellar cortex. Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D012118 Resorcinols A water-soluble crystalline benzene-1,3-diol (resorcinol) and its derivatives. m-Dihydroxybenzenes,meta-Dihydroxybenzenes,m Dihydroxybenzenes,meta Dihydroxybenzenes
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
D002525 Cerebellar Cortex The superficial GRAY MATTER of the CEREBELLUM. It consists of two main layers, the stratum moleculare and the stratum granulosum. Cortex Cerebelli,Cerebelli, Cortex,Cerebellus, Cortex,Cortex Cerebellus,Cortex, Cerebellar
D003515 Cycloleucine An amino acid formed by cyclization of leucine. It has cytostatic, immunosuppressive and antineoplastic activities. 1-Aminocyclopentanecarboxylic Acid,Aminocyclopentanecarboxylic Acid,NSC 1026,1 Aminocyclopentanecarboxylic Acid,Acid, 1-Aminocyclopentanecarboxylic,Acid, Aminocyclopentanecarboxylic
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic

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