Sodium signals in cerebellar Purkinje neurons and Bergmann glial cells evoked by glutamatergic synaptic transmission

Abstract

Glial cells express specific high-affinity transporters for glutamate that play a central role in glutamate clearance at excitatory synapses in the brain. These transporters are electrogenic and are mainly energized by the electrochemical gradient for sodium. In the present study, we combined somatic whole-cell patch-clamp recordings with quantitative Na+ imaging in fine cellular branches of cerebellar Bergmann glial cells and in dendrites of Purkinje neurons to analyze intracellular Na+ signals close to activated synapses. We demonstrate that pressure application of glutamate and glutamate agonists causes local Na+ signals in the mM range. Furthermore, we analyzed the pharmacological profile, as well as the time course and spatial distribution of Na+ signals following short synaptic burst stimulation of parallel or climbing fibers. While parallel fibers stimulation resulted in local sodium transients that were largest in processes close to the stimulation pipette, climbing fibers stimulation elicited global sodium transients throughout the entire cell. Glial sodium signals amounted to several mM, were mainly caused by sodium influx following inward transport of glutamate and persisted for tens of seconds. Sodium transients in dendrites of Purkinje neurons, in contrast, were mainly caused by activation of AMPA receptors and had much faster kinetics. By reducing the driving force for sodium-dependent glutamate uptake, intracellular sodium accumulation in glial cells upon repetitive activity might provide a negative feedback mechanism, promoting the diffusion of glutamate and the activation of extrasynaptic glutamate receptors at active synapses in the cerebellum.

GABA uptake-dependent Ca 2+ signaling in developing olfactory bulb astrocytes

“…Application of 300 M and 600 M GABA evoked Na ϩ rises of 2.2 Ϯ 0.1 mM (n ϭ 74/3/2) and 3.2 Ϯ 0.1 mM (n ϭ 188/6/3), respectively, in the cell bodies (Fig. 3C), which corresponds to transporter-mediated Na ϩ transients in other glial cells (22). Larger Na ϩ transients are expected in the fine astrocyte processes due to the larger surface-to-volume ratio (22), but the detector noise rendered SBFI fluorescence recordings impossible in astrocytic processes.…”

“…3C), which corresponds to transporter-mediated Na ϩ transients in other glial cells (22). Larger Na ϩ transients are expected in the fine astrocyte processes due to the larger surface-to-volume ratio (22), but the detector noise rendered SBFI fluorescence recordings impossible in astrocytic processes. Concentrations of 100 M and 600 M nipecotic acid evoked Na ϩ rises with an amplitude of 1.8ϩ/Ϫ0.1 mM (n ϭ 47/3/2) and 2.3ϩ/Ϫ0.1 mM (n ϭ 84/3/2), respectively.…”

Action Potential Firing Induces Sodium Transients in Macroglial Cells of the Mouse Corpus Callosum

“…In grey matter astrocytes of the mouse hippocampus, activity-related sodium transients are mainly due to activation of glutamate transport [4], while in cerebellar Bergman glial cells, an additional contribution of AMPA receptors was described [6]. To study the relevance of glutamate transporter versus glutamate receptor-mediated sodium influx into macroglial cells of the corpus callosum, we performed experiments in which axons were stimulated repetitively while different blockers were added successively (N = 12).…”

“…A major pathway for the generation of these astrocyte sodium transients is the activation of sodium-dependent glutamate uptake in response to synaptic release of glutamate [3][4][5][6][7]. Glutamate uptake by grey matter astrocytes is realized by two transporter subtypes, namely glutamate transporter 1 (GLT-1) and glutamate-aspartate transporter (GLAST) [8,9].…”

Astroglial calcium signalling in Alzheimer's disease

“…It appeared that stimulation of astrocytes with neurotransmitters released from neuronal terminals triggers long lasting elevation of cytosolic Na + ([Na + ] i ) with amplitudes of 5 -20 mM [58][59][60][61]; this [Na + ] i increase resulted from Na + entry through plasmalemmal channels (mainly ionotropic receptors) and transporters (mainly Na + -dependent glutamate transporters). Astroglial Na + signals are also able to spread trough astroglial syncytia in a form of propagating waves; this propagation is mediated by connexin channels forming gap junctions [62].…”