Sodium signals in cerebellar Purkinje neurons and Bergmann glial cells evoked by glutamatergic synaptic transmission.
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.
Bennay
Mustapha
M
Institute for Neurobiology, Geb. 26.02.00, Universitaetsstrasse 1, Heinrich-Heine-University of Duesseldorf, Duesseldorf, Germany.
Langer
Julia
J
Meier
Silke D
SD
Kafitz
Karl W
KW
Rose
Christine R
CR
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018698:Glutamic Acid; D012964:Sodium