Both Neurons and Astrocytes Exhibited Tetrodotoxin-Resistant Metabotropic Glutamate Receptor-Dependent Spontaneous Slow Ca2+ Oscillations in Striatum

Abstract

The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca2+ signaling. To characterize Ca2+ signaling in striatal cells, spontaneous cytoplasmic Ca2+ transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP) in the astrocytes. In both the GFP-negative cells (putative-neurons) and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca2+ transients (referred to as slow Ca2+ oscillations), which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca2+ oscillation. Depletion of the intracellular Ca2+ store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca2+ oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca2+ oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca2+ oscillation in both putative-neurons and astrocytes. The slow Ca2+ oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca2+ oscillation may involve in the neuron-glia interaction in the striatum.

Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations

“…TTX specifically inhibits voltage-gated Na + channels but does not impinge on the functionality of other types of Na + channels present in glioma cells ( 21 , 22 ). PcTX-1 is a specific inhibitor of ASICs.…”

Low frequency electric current noise in glioma cell populations

“…Tetrodotoxin (TTX) specifically inhibits the voltage-gated Na + channels 26 and does not impinge on the functionality of other various types of Na + channels present in glia cells. 27 Fig . 3 illustrates the effect of adding 1 mM of TTX to a population of freshly deposited adherent C6 glioma cells.…”

Store-Operated Calcium Channels Are Involved in Spontaneous Slow Calcium Oscillations in Striatal Neurons

“…The very long-lasting [Ca 2+ ] i elevations that we observed in the form of spontaneous slow Ca 2+ oscillations in the striatum (Osanai et al, 2006;Tamura et al, 2014) led us to hypothesize that Ca 2+ in the ER may be depleted and that SOCCs may then be opened when the slow Ca 2+ oscillations occur. This opening of SOCCs may be involved in the mechanism of maintaining high [Ca 2+ ] i for a long time in striatal neurons exhibiting these slow Ca 2+ oscillations.…”

“…However, the cellular Ca 2+ signaling in striatal neurons still remains unclear. We previously reported long-lasting spontaneous intracellular Ca 2+ oscillations in rodent striatal neurons (Osanai et al, 2006;Tamura et al, 2014), which lasted as long as 300 s. These slow Ca 2+ oscillations were not induced by action potentials, but by Ca 2+ release from the ER. Although both the metabotropic glutamate receptor type 5 and inositol 1,4,5-trisphosphate receptor (mGluR5-IP3R) signal transduction cascade were involved in these slow Ca 2+ oscillations (Tamura et al, 2014), an important issue arises as to how such a long elevation in Ca 2+ is maintained.…”

“…The methods for Ca 2+ imaging were described previously (Osanai et al, 2006;Tamura et al, 2014;Kikuta et al, 2015). Briefly, postnatal day 12 (P12) to P17 GAD67-GFP mice of either sex were anesthetized with isoflurane (Mylan) and decapitated.…”