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Depression of synaptic transmission and evoked NMDA Ca 2+ influx in hippocampal neurons by adenosine and its blockade by LTP or ischemia
Author(s) -
Schubert Peter,
Keller Franz,
Rudolphi Karl
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280339
Subject(s) - nmda receptor , long term potentiation , neurotransmission , neuroscience , adenosine , chemistry , synaptic plasticity , postsynaptic potential , hippocampal formation , biophysics , biology , endocrinology , receptor , biochemistry
Abstract Neuronal Ca 2+ influx in response to repetitive synaptic activation was determined in rat hippocampal slices by measuring the evoked decreases of the extracellular Ca 2+ concentration with ion‐sensitive electrodes in the synaptic layer (ΔCaSpad) and in the CA 1 pyramidal cell layer (ΔCaSpyr). The generation of NMDA receptor‐mediated Ca 2+ fluxes (NMDA Ca 2+ fluxes) was uncovered by measuring the proportion of ΔCa blocked by the NMDA receptor antagonist 2‐amino‐5‐phosphonovalerate (APV); 1 μmol adenosine increased the critical input frequency required to generate synaptic MNDA Ca 2+ influx. This effect is apparently exerted by limiting the postsynaptic membrane depolarization and is no longer seen, if the NMDA Ca 2+ channels have lost their Mg‐dependent voltage sensitivity. It has been recently reported by Ben‐Ari and co‐workers [(1992) Trends Neurosci 15:333–339] that such a loss of voltage sensitivity, leading to an “upregulation” and persistent generation of NMDA Ca 2+ currents, Can be elicited by an activation of the protein kinase C (PKC) and may be responsible for the initiation of synaptic long‐term potentiation (LTP) and for ischemia‐induced nerve cell damage. Consistent with this hypothesis, we found that the depressive effect of 1 μmol adenosine on the generation of NMDA Ca 2+ influx or synaptic transmission can be no longer elicited in hippocampal slices after LTP and after preceding transient brain ischemia in vivo. These findings suggest that the mosaic of different adenosine actions includes some which are related to PKC activation. Accordingly, we observed a synaptic modulation by adenosine which was characterized by a reduced Mg‐sensitivity and blocked by phorbol ester treatment. © 1993 Wiley‐Liss, Inc.