Two distinct modalities of NMDA‐receptor inactivation induced by calcium influx in cultured rat hippocampal neurons

FEBS Letters

Montal, Mauricio¹  Schinder, Alejandro F.¹ 

[1] Department of Biology, University of California San Diego, La Jolla, CA 92093-0319, USA

关键词: Glutamate receptor;    Ionic channel;    Receptor modulation;    Synaptic transmission;    Signal transduction;    BSS;    balanced salt solution;    [Ca2+ e;    extracellular calcium concentration;    [Ca2+]i;    intracellular calcium concentration;    FUDR;    5-fluoro-2'-deoxyuridine;    glu;    glutamate;    I;    current;    i;    inactivation;    LTP;    long term potentiation;    MK-801;    (+)-5-methyl-10;    11-dihydro-5H-dibenzo[a;    d]cyclohepten-5;    10-im ine maleate;    n;    number of experiments;    NMDA;    N-methyl-d-aspartate;    P;    peak current;    R;    receptor;    S;    steady state current;    V;    voltage;   

DOI  :  10.1016/0014-5793(93)80480-I

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Repetitive stimulation of glutamate (glu) receptors elicits increasingly smaller ionic currents in hippocampal neurons. To investigate mechanisms underlying this phenomenon, voltage clamp whole-cell currents evoked by glu (100 μM) were recorded from hippocampal neurons in culture. These currents were primarily carried by N-methyl-d-aspartate-receptor (NMDA-R) channels, as shown by the voltage-dependent sensitivity to extracellular Mg²⁺ blockade, and inhibition by the specific antagonist MK-801. In the presence of 2.2 mM extracellular Ca²⁺ ([Ca²⁺]_e, repetitive glu applications (15 episodes of 4 s/min) elicited progressively smaller currents that stabilized at 45% of their initial peak value. Replacement of [Ca²⁺ _e, by Ba²⁺ produced similar effects. This phenomenon, defined as interepisode inactivation, was exacerbated by elevating [Ca²⁺]_e to 11 mM, attenuated by reducing [Ca²⁺ _e to 0.22 mM, and further diminished by shortening the length of the glu pulse to 2 s. Current decay exhibited during individual stimuli, or intraepisode inactivation, was dependent on [Ca²⁺]_e yet remained stable during repetitive stimulation. We conclude that interepisode and intraepisode inactivations of NMDA-R currents are the expression of two distinct processes triggered by Ca²⁺. These modalities of inactivation may arise from Ca²⁺ binding either to the receptor or to closely associated regulatory proteins.

【 授权许可】

Unknown