Synaptic activity augments muscarinic acetylcholine receptor-stimulated inositol 1,4,5-trisphosphate production to facilitate Ca2+ release in hippocampal neurons.
Intracellular Ca2+ store release contributes to activity-dependent synaptic plasticity in the central nervous system by modulating the amplitude, propagation, and temporal dynamics of cytoplasmic Ca2+ changes. However, neuronal Ca2+ stores can be relatively insensitive to increases in the store-mobilizing messenger inositol 1,4,5-trisphosphate (IP3). Using a fluorescent biosensor we have visualized M1 muscarinic acetylcholine (mACh) receptor signaling in individual hippocampal neurons and observed increased IP3 production in the absence of concurrent Ca2+ store release. However, coincident glutamate-mediated synaptic activity elicited enhanced and oscillatory IP3 production that was dependent upon ongoing mACh receptor stimulation and S-alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid receptor activation of Ca2+ entry. Moreover, the enhanced levels of IP3 now mobilized Ca2+ from intracellular stores that were refractory to the activation of mACh receptors alone. We conclude that convergent ionotropic and metabotropic receptor inputs can facilitate Ca2+ signaling by enhancing IP3 production as well as augmenting release by Ca2+-induced Ca2+ release.
Nash
Mark S
MS
Department of Cell Physiology & Pharmacology, University of Leicester, Maurice Shock Medical Sciences Building, University Road, Leicester, LE1 9HN, United Kingdom.
Willets
Jonathon M
JM
Billups
Brian
B
John Challiss
R A
RA
Nahorski
Stefan R
SR
D000818:Animals; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005456:Fluorescent Dyes / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D009991:Oscillometry; D010852:Picrotoxin / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D002118:Calcium; D005456:Fluorescent Dyes; D018698:Glutamic Acid; D049452:Green Fluorescent Proteins; D015544:Inositol 1,4,5-Trisphosphate; D010852:Picrotoxin; D018091:Receptors, AMPA; D011976:Receptors, Muscarinic; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid