Calcium signaling of glial cells along mammalian axons.
Glial [Ca2+]i signaling was examined in a mammalian white matter lacking neuronal cell bodies and synapses. Rat optic nerves (postnatal days 2 and 7) were stained with calcium indicator dyes and confocal images of [Ca2+bdi were recorded at approximately 25 degrees C or approximately 37 degrees C. Glial cell bodies showed spiking or sustained [Ca2+], response to bath-applied glutamate (50-500 microM). The metabotropic glutamate agonist trans-ACPD elicited transient, sometimes spiking, [Ca2+], responses, whereas ionotropic agonists kainate and AMPA elicited a 6,7-dinitroquinoxaline-2,3-dione-sensitive, mostly sustained [Ca2+]i response. Transient and spiking glial [Ca2+]i responses also were elicited by adenosine and ATP (0.1-100 microM). Repetitive nerve stimulation (10-20 Hz) elicited [Ca2+bdi spiking in 15-25% of glial cells in postnatal day 7 nerves, with spiking typically occurring 15-60 sec after onset of nerve stimulation. At 37 degrees C, the frequency of glial [Ca2+]i spikes increased from approximately 0.06 Hz to approximately 0.11 Hz when axonal stimulation was increased from 10 to 20 Hz. This activity-dependent glial spiking was inhibited by TTX, could not be mimicked by increasing the bath K+ by 20 mM, and occurred when nerves were stimulated in the absence of bath calcium. Activity-dependent and glutamate-induced glial spiking could be mimicked by altering ionic gradients known to favor release of glutamate via glutamate transporters, including elevation of intracellular Na+ by veratridine concurrent with external K+ elevation. We suggest that glial [Ca2+]i spiking observed during electrical activity resulted from activation of glial receptors (e.g., metabotropic glutamate receptor, adenosine receptor) by substances (e.g., glutamate, adenosine) released from the optic nerve in a nonvesicular fashion, possibly through a reversal of sodium-coupled transporters when Na+ and K+ gradients are altered by prolonged nerve activity.
Kriegler
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Biophysics Training Program, University of Wisconsin, Madison 53706.
Chiu
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D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000814:Aniline Compounds; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008959:Models, Neurological; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009900:Optic Nerve / Q000254:growth & development / Q000502:physiology*; D015398:Signal Transduction; D013779:Tetrodotoxin / Q000494:pharmacology; D014966:Xanthenes; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000814:Aniline Compounds; D005456:Fluorescent Dyes; D005971:Glutamates; D014966:Xanthenes; C059715:Fluo-3; D018698:Glutamic Acid; D013779:Tetrodotoxin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium