Regulation of spontaneous Ca²⁺ spikes by metabotropic glutamate receptors in primary cultures of rat cortical neurons

Abstract

Periodic and spontaneous Ca 21 spikes are observed in neurons during development of the central nervous system, and spontaneous changes in intracellular Ca 21 concentration in neurons play important roles in the development of neural circuits. To clarify the roles of metabotropic glutamate receptors (mGluRs) in the regulation of spontaneous Ca 21 spikes, we investigated the effects of selective and nonselective mGluRs ligands on primary cultures of rat cortical neurons. Cultured cortical neurons expressed all eight mGluR subtypes on reverse transcription-PCR. The mGluR2 and mGluR3 agonists LY379268, LY354740, and (2R,4R)-APDC increased the amplitude but decreased the frequency of spontaneous Ca 21 spikes in cultured cortical neurons. The effects of these mGluR2 and mGluR3 agonists were completely inhibited by the presence of a potent mGluR2 and mGluR3 antagonist, LY341495, and by pretreatment with pertussis toxin. No significant effect was observed with either activation or inhibition of mGluR1, mGluR4, mGluR5, mGluR6, mGluR7, and mGluR8 on the spontaneous Ca 21 spikes in cultured cortical neurons. These findings indicate that, among mGluRs, the group II mGluR subtypes mGluR2 and mGluR3 play principal roles in modulation of spontaneous Ca 21 spikes. V V C 2010 Wiley-Liss, Inc.

Nanomolar Bifenthrin Alters Synchronous Ca2+Oscillations and Cortical Neuron Development Independent of Sodium Channel Activity

“…This finding is consistent with previous reports that have demonstrated Glu receptor signaling pathways regulate SCO behavior (Dravid and Murray, 2004;Koga et al, 2010). We also show that both competitive and noncompetitive N-methyl-D-aspartate receptor antagonists (AP5 and MK-801) suppress both basal and bifenthrinaugmented SCO activity.…”

Rapid Throughput Analysis Demonstrates that Chemicals with Distinct Seizurogenic Mechanisms Differentially Alter Ca2+ Dynamics in Networks Formed by Hippocampal Neurons in Culture

“…SCOs in cultured neuronal networks are dependent on action potentials and the release of synaptic neurotransmitter vesicles (Dravid and Murray, 2004). A number of studies have suggested that SCO activity is highly dependent on the balance of ongoing excitatory ionotropic glutamatergic and inhibitory GABAergic neurotransmission within the neuronal network (Dravid and Murray, 2004;George et al, 2009, Koga et al, 2010Pacico and Mingorance-Le Meur, 2014). In addition to ionotropic Glu receptors, both type I and type II metabotropic Glu receptors also modulate SCO patterns (Dravid and Murray, 2004;Koga et al, 2010).…”

“…A number of studies have suggested that SCO activity is highly dependent on the balance of ongoing excitatory ionotropic glutamatergic and inhibitory GABAergic neurotransmission within the neuronal network (Dravid and Murray, 2004;George et al, 2009, Koga et al, 2010Pacico and Mingorance-Le Meur, 2014). In addition to ionotropic Glu receptors, both type I and type II metabotropic Glu receptors also modulate SCO patterns (Dravid and Murray, 2004;Koga et al, 2010). For example, positive allosteric modulators of GABA A receptors (GABA A R), such as diazepam or allopregnanolone, decreased SCO amplitude and frequency and acted synergistically (Cao et al, 2012).…”

Initial Phase of Neuropathic Pain within a Few Hours after Nerve Injury in Mice

“…The changes in the spinal neural circuits were triggered by disruption of the afferent basal firing, and this effect was mimicked by the application of a group II mGluR antagonist, while the agonists are known to produce alleviating effects on neuropathic pain (Simmons et al, 2002;Jones et al, 2005). Activation of group II mGluRs reduces presynaptic transmitter release (Goudet et al, 2009), hyperpolarizes postsynaptic neurons by opening G-protein-coupled inward rectifier K ϩ channels (Irie et al, 2006;Lee and Sherman, 2009), and modulates spontaneous Ca 2ϩ spikes (Koga et al, 2010). Stimulation of the M/U and R/Mc nerves produced fluorescence increases in the same cortical area (data not shown).…”