Effect of calcium on the uptake of glutamate by synaptosomes: possible involvement of two different mechanisms.
The effects of Ca2+ on glutamate uptake by synaptosomes were investigated. Glutamate uptake was decreased in the absence of Ca2+ with 2 mM EGTA added to the medium. After a 8-min preincubation, the uptake reduced to the greatest extent (about 64% of the uptake measured in Ca2+ medium). According to the kinetic analysis, lack of Ca2+ resulted in a reduction of the Vmax for glutamate uptake. These results suggested external Ca2+ was necessary for the optimal uptake of glutamate. TTX, an inhibitor of the voltage-dependent Na+ channel, almost reversed the reduction of glutamate uptake, indicating that the uptake might be impaired via the partial activation of the voltage-dependent tetrodotoxin-sensitive Na+ channel. On the other hand, glutamate uptake was decreased by trifluoperazine, a calmodulin antagonist, and KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, implying that intrasynaptosomal Ca2+ might also have a role in the uptake of glutamate, and Ca2+/calmodulin-dependent processes, such as Ca2+/calmodulin-dependent protein kinase II, might be involved in the modulation of glutamate transporter activity.
Zhu
B G
BG
Department of Physiology, Institute of Neuroscience, Second Military Medical University, Shanghai, PR China.
Chen
Y Z
YZ
Xing
B R
BR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002540:Cerebral Cortex / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014268:Trifluoperazine; D018698:Glutamic Acid; D013779:Tetrodotoxin; D004533:Egtazic Acid; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium