Calcitonin gene-related peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices.
The neuropeptide calcitonin gene-related peptide (CGRP) is transiently expressed in cerebellar climbing fibers during development while its receptor is mainly expressed in astrocytes, in particular Bergmann glial cells. Here, we analyzed the effects of CGRP on astrocytic calcium signaling. Mouse cultured astrocytes from cerebellar or cerebral cortex as well as Bergmann glial cells from acutely isolated cerebellar slices were loaded with the Ca(2+) sensor Fura-2. CGRP triggered transient increases in intracellular Ca(2+) in astrocytes in culture as well as in acute slices. Responses were observed in the concentration range of 1 nm to 1 mm, in both the cell body and its processes. The calcium transients were dependent on release from intracellular stores as they were blocked by thapsigargin but not by the absence of extracellular calcium. In addition, after CGRP application a further delayed transient increase in calcium activity could be observed. Finally, cerebellar astrocytes from neonatal mice expressed receptor component protein, a component of the CGRP receptor, as revealed by immunofluorescence and confocal microscopy. It is thus proposed that the CGRP-containing afferent fibers in the cerebellum (the climbing fibers) modulate calcium in astrocytes by releasing the neuropeptide during development and hence possibly influence the differentiation of Purkinje cells.
Morara
Stefano
S
C. N. R., Institute of Neuroscience, Via Privata Bianco 9, 20131 Milan, Italy. stefano.morara@in.cnr.it
Wang
Li-Ping
LP
Filippov
Vitaly
V
Dickerson
Ian M
IM
Grohovaz
Fabio
F
Provini
Luciano
L
Kettenmann
Helmut
H
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2; D007202:Indicators and Reagents; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
C491562:Crcp protein, rat; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D018015:Receptors, Calcitonin Gene-Related Peptide; D019284:Thapsigargin; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium; D016257:Fura-2