Effect of calcium on the uptake of glutamate by synaptosomes: possible involvement of two different mechanisms

• Published in: Journal of Neural Transmission Vol. 106; no. 3-4; pp. 257 - 264
• Main Authors: Zhu, B G, Chen, Y Z, Xing, B R
• Format: Journal Article
• Language: English
• Published: Austria 01.01.1999
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Animals; Calcium - pharmacology; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Calmodulin - antagonists & inhibitors; Cerebral Cortex - metabolism; Chelating Agents - pharmacology; Egtazic Acid - pharmacology; Electrophysiology; Enzyme Inhibitors - pharmacology; Glutamic Acid - pharmacokinetics; Male; Rats; Rats, Sprague-Dawley; Sodium Channel Blockers; Sodium Channels - physiology; Synaptosomes - drug effects; Synaptosomes - metabolism; Tetrodotoxin - pharmacology; Trifluoperazine - pharmacology
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s007020050155

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.