Repeated NMDA receptor activation induces distinct intracellular calcium changes in subpopulations of striatal neurons in vitro.
The mechanisms underlying long-term calcium changes evoked by excitatory amino acids have not been previously examined in striatal neurons. Fura-2 fluorescence measurements were used to examine intracellular calcium concentration ([Ca2+]i) changes due to repeated N-methyl-D-aspartate (NMDA) receptor activation, in primary cultures of murine striatal neurons. Three applications of 200 microM NMDA (for 2 min, each application separated by 7 min), in 0 magnesium-containing artificial cerebral spinal fluid, elicited three distinct responses. In 50 +/- 8% of the NMDA-responsive neurons, no persistent increases in [Ca2+]i (final [Ca2+]i < or = 150% baseline) were observed, while in 33 +/- 7% and 17 +/- 3% of the cells, sustained (peak response > final [Ca2+]i > 150% baseline) and uncontrolled increases (final [Ca2+]i > or = peak response) were observed, respectively. NMDA-responsive neurons that were intensely immunoreactive for the calcium binding protein calbindin-D28k never exhibited uncontrolled increases in [Ca2+]i. Removal of extracellular Ca2+ significantly attenuated sustained, but not uncontrolled, increases in [Ca2+]i; sustained increases in some neurons were also attenuated by application of verapamil (100 microM) or MK-801 (1 microM). Pre-treatment of striatal neurons with the protein kinase C blocker sphingosine (20 microM), virtually eliminated the development of sustained or uncontrolled increases in [Ca2+]i. These findings suggest that specific intracellular mechanisms regulate the distinct [Ca2+]i responses of subpopulations of striatal neurons to repeated NMDA receptor activation.
Weiss
S
S
Neuroscience Research Group, University of Calgary Faculty of Medicine, Alta., Canada.
Hochman
D
D
MacVicar
B A
BA
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D064030:S100 Calcium Binding Protein G / Q000032:analysis
C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D016194:Receptors, N-Methyl-D-Aspartate; D064030:S100 Calcium Binding Protein G; D011493:Protein Kinase C; D002118:Calcium