N-methyl-d-aspartate receptor-mediated, calcium-induced calcium release in rat dentate gyrus/CA4 in vivo

✍ Scribed by Jerzy W. Lazarewicz; Waldemar Rybkowski; Apolonia Ziembowicz; Mohol Alaraj; Marcin Sadowski; Jerzy Wegiel; Henryk M. Wisniewski

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 189 KB
• Volume: 51
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19980101)51:1<76::aid-jnr8>3.0.co;2-i

✦ Synopsis

Previously, by using in vivo microdialysis, we demonstrated a huge release of 45Ca2+ from prelabeled tissues to dialysate that was evoked by application of N-methyl-D-aspartate (NMDA) to the rat dentate gyrus (DG) and sector 4 of the cornu ammonis. To establish the mechanism of this phenomenon, in the present study, we characterized its NMDA receptor dependence, investigated the mechanism of 45Ca2+ removal from the cells, and evaluated the possible involvement of calcium-binding protein calbindin D28k and of ryanodine receptors. Microdialysis experiments demonstrated a dose-response relation between NMDA and 45Ca2+ release and sensitivity of this phenomenon to inhibition by 10 microM MK-801 and 5 mM 5-(N,N-dimethyl)-amiloride, thus indicating the NMDA receptor dependence and a role of Na+/Ca2+ exchanger in mediating 45Ca2+ release from cells. Immunocytochemical experiments confirmed that DG granule cells in the investigated inbred rat strain are strongly calbindin D28k-immunopositive, indicating probable involvement of this protein. However, microdialysis studies demonstrated that NMDA-evoked 45Ca2+ release was suppressed by 100 microM dantrolene and 250 microM ryanodine, whereas 50 microM ryanodine stimulated this effect. This points to a key role in the investigated phenomenon of calcium-induced calcium release (CICR) via ryanodine receptors. To our knowledge, this is the first in vivo demonstration of NMDA-evoked CICR. We postulate the usefulness of microdialysis in such studies.