title: L-glutamate-induced changes in intracellular calcium oscillation frequency through non-classical glutamate receptor binding in cultured rat myocardial cells.
abstract: The effects of L-glutamate, N-methyl-D-aspartate (NMDA), kainate (KA) and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) on intracellular Ca2+ oscillation frequency were studied in cultured rat myocardial cells. Ca2+ oscillations per minute were increased as compared to control by L-glutamate (100 microM) from 3.8 +/- 2.2 to 25.7 +/- 4.3 (p < 0.001) and the NMDA-receptor agonist, NMDA (100 microM), from 1.2 +/- 0.8 to 34.8 +/- 10.1 (p < 0.011). Increases over control frequency were also seen in response to the non-NMDA receptor agonists KA (100 microM) from 5.8 +/- 2.3 to 25.6 +/- 3.2 (p < 0.001) and AMPA (10 microM) from 3.8 +/- 1.2 to 13.3 +/- 1.8 (p < 0.001). The non-competitive NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801) (10 microM), decreased the Ca2+ oscillation frequency induced by NMDA (100 microM from 36.8 +/- 12.2 to 7.2 +/- 7.2 (p < 0.05). (+/-)-2-Amino-7-phosphonoheptanoic acid (AP7), a competitive inhibitor at the NMDA receptor inhibited the increase in frequency induced by KA (100 microM) at all concentrations tested (0.1, 1.0, 10 and 100 microM). 6,7-Dinitroquinoxaline-2,3-dione (DNQX), a competitive inhibitor at non-NMDA receptors, also decreased the oscillation frequency elicited by KA (100 microM) from 35.4 +/- 9.4 to 28.2 +/- 9.8, 24.8 +/- 9.8 and 11 +/- 9.5 at concentrations of 0.1, 1.0 and 10 microM respectively. The peak amount of intracellular Ca2+ as expressed as the fluo 3 ratio, F/Frcst, was not increased by L-glutamate, NMDA or KA. These results suggest the presence of a novel glutamate receptor composed of both non-NMDA and NMDA subunits on cultured rat myocardial cells, and receptor stimulation leads to an increase in intracellular Ca2+ oscillation frequency.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D007424:Intracellular Fluid / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D002118:Calcium