Visualization of IP(3) dynamics reveals a novel AMPA receptor-triggered IP(3) production pathway mediated by voltage-dependent Ca(2+) influx in Purkinje cells.
IP(3) signaling in Purkinje cells is involved in the regulation of cell functions including LTD. We have used a GFP-tagged pleckstrin homology domain to visualize IP(3) dynamics in Purkinje cells. Surprisingly, IP(3) production was observed in response not only to mGluR activation, but also to AMPA receptor activation in Purkinje cells in culture. AMPA-induced IP(3) production was mediated by depolarization-induced Ca(2+) influx because it was mimicked by depolarization and was blocked by inhibition of the P-type Ca(2+) channel. Furthermore, trains of complex spikes, elicited by climbing fiber stimulation (1 Hz), induced IP(3) production in Purkinje cells in cerebellar slices. These results revealed a novel IP(3) signaling pathway in Purkinje cells that can be elicited by synaptic inputs from climbing fibers.
Okubo
Y
Y
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kakizawa
S
S
Hirose
K
K
Iino
M
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001798:Blood Proteins / Q000235:genetics / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005822:Genetic Vectors; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000493:pharmacokinetics; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010750:Phosphoproteins / Q000235:genetics / Q000493:pharmacokinetics; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012845:Sindbis Virus / Q000235:genetics; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D001565:Benzoates; D001798:Blood Proteins; D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D018696:Neuroprotective Agents; D010750:Phosphoproteins; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C039077:platelet protein P47; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D005998:Glycine