Abstract
Calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs), as well as NMDARs, play a pivotal role in plasticity and in regulating neurotransmitter release. Here we visualized in the mature hippocampal neuroglial cultures the neurons expressing CP-AMPARs and CP-KARs. These neurons were visualized by a characteristic fast sustained [Ca2+]i increase in response to the agonist of these receptors, domoic acid (DoA), and a selective agonist of GluK1-containing KARs, ATPA. Neurons from both subpopulations are GABAergic. The subpopulation of neurons expressing CP-AMPARs includes a larger percentage of calbindin-positive neurons (39.4 ± 6.0%) than the subpopulation of neurons expressing CP-KARs (14.2 ± 7.5% of CB+ neurons). In addition, we have shown for the first time that NH4Cl-induced depolarization faster induces an [Ca2+]i elevation in GABAergic neurons expressing CP-KARs and CP-AMPARs than in most glutamatergic neurons. CP-AMPARs antagonist, NASPM, increased the amplitude of the DoA-induced Ca2+ response in GABAergic neurons expressing CP-KARs, indicating that neurons expressing CP-AMPARs innervate GABAergic neurons expressing CP-KARs. We assume that CP-KARs in inhibitory neurons are involved in the mechanism of outstripping GABA release upon hyperexcitation.
Highlights
Published: 27 November 2021Kainate (KA) and AMPA receptors are ligand-gated channels permeable for Na+ and particular subtypes of KA and AMPA receptors are permeable for Ca2+ .The Ca2+ influx through these receptors can induce neurotransmitter release without the contribution of NMDARs and voltage-gated calcium channels [1].Calcium-permeable KA receptors (CP-KARs) contain unedited GluK1 or GluK2 subunits [2,3]
Further application of AMPAR/KAR agonist, domoic acid (DoA) (300 nM) (Figure 1A), induces a rapid [Ca2+ ]i increase in ATPA-sensitive neurons (6 ± 1% of neurons) and [Ca2+ ]i oscillations with a delay of 17 ± 4 s in most other neurons
We stained the cells with antibodies against GABA and neuron-specific enolase (NSE) to demonstrate that ATPA increases [Ca2+ ]i only in GABAergic neurons expressing CP-KARs
Summary
The Ca2+ influx through these receptors can induce neurotransmitter release without the contribution of NMDARs and voltage-gated calcium channels [1]. Calcium-permeable KA receptors (CP-KARs) contain unedited GluK1 or GluK2 subunits [2,3]. Most studies show that GluK1-containing KARs localize on GABAergic neurons in presynaptic terminals [3,7,8,9]. Activation of GluK1-containing kainate receptors may promote the GABA release from interneurons, leading to suppression of neuronal network activity. Contribution of GluK1-expressing GABAergic neurons in the suppression of hyperexcitation was obtained both in in vivo and in vitro experiments. Xu and coauthors demonstrated the neuroprotective effect of a selective GluK1-containing KARs agonist, ATPA, against ischemia-reperfusion-induced neuronal cell death in in vivo studies [10,11]
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