Referenced in: none

Automatically associated channels: Kir2.3

Title: 35 mM K(+)-stimulated 45Ca2+ uptake in cerebellar granule cell cultures mainly results from NMDA receptor activation.

Authors: M Didier, M Héaulme, N Gonalons, P Soubrie, J Bockaert, J P Pin

Journal, date & volume: Eur. J. Pharmacol., 1993 Jan 4 , 244, 57-65

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7678398

Abstract
In primary cultures of cerebellar granule cells, the Ca2+ influx resulting from K+ depolarization (35 mM) was equal to one-third of that observed with 100 microM N-methyl-D-aspartate (NMDA) and was reduced in a major part (90%) by NMDA receptor antagonists. The rank order of potency of these competitive and non-competitive NMDA receptor antagonists was very close to their affinity for the NMDA and phencyclidine sites respectively. Granular cell depolarization with 35 mM K+ also induced a large increase in the extracellular glutamate concentration. Repeated washes of the culture wells, addition of glutamate pyruvate transaminase (+2 mM pyruvate), or pretreatment of the cells with tetanus toxin resulted in a parallel reduction of the extracellular glutamate concentration and 45Ca2+ uptake measured after a 35 mM K+ stimulation. Dihydropyridine (BAY K-8644) stimulated the release of glutamate in a nifedipine-sensitive manner in the presence of 15 mM K+. However, nifedipine (1 microM), which decreased by 60% the K(+)-induced 45Ca2+ uptake, did not reduce the 35 mM K(+)-evoked glutamate release. Taken together, these results demonstrated that in cerebellar granule cell cultures, 90% of the 35 mM K(+)-stimulated 45Ca2+ influx resulted from the release of glutamate and the consecutive activation of NMDA receptors. Activation of these glutamate receptors then allows Ca2+ influx to occur through L-type voltage-operated Ca2+ channels.