Document Detail


L-glutamate-induced changes in intracellular calcium oscillation frequency through non-classical glutamate receptor binding in cultured rat myocardial cells.
MedLine Citation:
PMID:  7475942     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
C R Winter; R C Baker
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Life sciences     Volume:  57     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1995  
Date Detail:
Created Date:  1995-12-15     Completed Date:  1995-12-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1925-34     Citation Subset:  IM    
Affiliation:
University of Mississippi Medical Center, Department of Pharmacology and Toxicology, Jackson 39216, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism*
Cells, Cultured
Excitatory Amino Acid Agonists / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Glutamic Acid / pharmacology*
Heart / drug effects*,  innervation
Intracellular Fluid / metabolism
Kainic Acid / pharmacology
Myocardium / metabolism*,  ultrastructure
N-Methylaspartate / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Glutamate / drug effects,  metabolism*
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Grant Support
ID/Acronym/Agency:
AA07157/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Agonists; 0/Excitatory Amino Acid Antagonists; 0/Receptors, Glutamate; 0/Receptors, N-Methyl-D-Aspartate; 487-79-6/Kainic Acid; 56-86-0/Glutamic Acid; 6384-92-5/N-Methylaspartate; 7440-70-2/Calcium; 77521-29-0/alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

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