Coupling of glutamatergic receptors to changes in intracellular Ca2+ in rat cerebellar granule cells in primary culture

✍ Scribed by I. Holopainen; M. Louve; M. O. K. Enkvist; Prof. K. E. O. Akerman

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 661 KB
• Volume: 25
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490250206

✦ Synopsis

Changes in cytosolic free Ca2+ concentrations, [Ca2+Ii, in response to glutamate and glutamate receptor agonists were measured in rat cerebellar granule cells grown on coverslips. The intracellular Ca2+ as measured with fura-2 increased by applying kainate, N-methyl-D-aspartate (NMDA), quisqualate, and (RS)-d-amino-3-hydroxy-S-methyl-4-isoxazolepropionic (AMPA). When the extracellular Mg2+ was removed, the effects of NMDA and the NMDA receptor agonist cis-( &)-1 -amino-1,3-~yclopentanedicarboxylic acid (cis-ACPD) on intracellular CaZ+ were augmented. Glycine potentiated the effects of NMDA and cis-ACPD if the membrane was depolarized by increasing the extracellular K + concentration. The NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) abolished and the antagonist 3 4 [ +]-2-carboxypiperazin-4-yl)propyl-1phosphonic acid (CPP) greatly reduced the effect of NMDA in both the normal and the Mg-free media. The dose-response curves of NMDA and, to a lesser extent, of kainate were shifted to the left, and that of quisqualate became biphasic in the Mg-free medium.

The increase in [Ca' 'Ii produced by high quisqualate concentrations in the Mg-free medium was totally abolished by APS. The results suggest that Ca2+ influx in cerebellar granule cells occurs through both NMDA-and non-NMDA-coupled ion channels. A part of the quisqualate-induced rise in cytosolic Ca2 + seems to be linked to the activation of NMDA receptors.