Photochemically initiated intracellular astrocytic calcium waves in living mice using two-photon uncaging of IP(3).
We have developed a caged IP(3) analogue for two-photon photolysis in living animals. This probe is a cell permeable version and was coloaded with a fluorescent Ca(2+) dye into astrocytes in layer 1 of the somatosensory cortex of anesthetized mice. Two-photon irradiation of single cells at 720 nm produced rapid and robust increases in intracellular Ca(2+) concentrations monitored using two-photon microscopy at 950 nm. The photoevoked intracellular Ca(2+) waves were similar in magnitude to intrinsic signals in wild type mice. These waves did not propagate to other cells beyond the targeted astrocyte. In contrast, we observed intercellular astrocytic Ca(2+) waves in two mouse models of familial Alzheimer's disease. These data suggest that Alzheimer's might perturb gliotransmission but not IP(3) signaling per se in mouse models of the disease.
Department of Neuroscience, Mt. Sinai School of Medicine, One Gustave Levy Place, New York, New York, USA.
Sarah E
SE
Crowe
Srinivas
S
Kantevari
Graham C R
GC
Ellis-Davies
D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D020013:Calcium Signaling / Q000187:drug effects* / Q000528:radiation effects; D004195:Disease Models, Animal; D004950:Esterases / Q000378:metabolism; D005456:Fluorescent Dyes / Q000032:analysis; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D010782:Photolysis; D017785:Photons; D010841:Pia Mater / Q000648:ultrastructure; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics; D019076:Transgenes
C582856:2,3-O-cyclohexylidene-6-O-(ortho-nitroveratryl)-myo-inositol 1,4,5-trisphosphate hexakis(acetoxymethyl)ester; D005456:Fluorescent Dyes; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D015544:Inositol 1,4,5-Trisphosphate; D004950:Esterases