title: In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase.
abstract: Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases in neuronal activity. Inconsistent with this hypothesis, intact stimulus-induced vasodilation was observed in inositol 1,4,5-triphosphate (IP3) type-2 receptor (R2) knock-out (KO) mice, in which the primary mechanism of astrocytic calcium increase-the release of calcium from intracellular stores following activation of an IP3-dependent pathway-is lacking. Further, our results in wild-type (WT) mice indicate that in vivo onset of astrocytic calcium increase in response to sensory stimulus could be considerably delayed relative to the simultaneously measured onset of arteriolar dilation. Delayed calcium increases in WT mice were observed in both astrocytic cell bodies and perivascular endfeet. Thus, astrocytes may not play a role in the initiation of blood flow response, at least not via calcium-dependent mechanisms. Moreover, an increase in astrocytic intracellular calcium was not required for normal vasodilation in the IP3R2-KO animals.
authors: Neurosciences Graduate Program, University of California, San Diego, La Jolla, California 92093, USA.
authors: Krystal
authors: K
authors: Nizar
authors: Hana
authors: H
authors: Uhlirova
authors: Peifang
authors: P
authors: Tian
authors: Payam A
authors: PA
authors: Saisan
authors: Qun
authors: Q
authors: Cheng
authors: Lidia
authors: L
authors: Reznichenko
authors: Kimberly L
authors: KL
authors: Weldy
authors: Tyler C
authors: TC
authors: Steed
authors: Vishnu B
authors: VB
authors: Sridhar
authors: Christopher L
authors: CL
authors: MacDonald
authors: Jianxia
authors: J
authors: Cui
authors: Sergey L
authors: SL
authors: Gratiy
authors: Sava
authors: S
authors: Sakadzić
authors: David A
authors: DA
authors: Boas
authors: Thomas I
authors: TI
authors: Beka
authors: Gaute T
authors: GT
authors: Einevoll
authors: Ju
authors: J
authors: Chen
authors: Eliezer
authors: E
authors: Masliah
authors: Anders M
authors: AM
authors: Dale
authors: Gabriel A
authors: GA
authors: Silva
authors: Anna
authors: A
authors: Devor
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D006934:Hypercalcemia / Q000503:physiopathology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000172:deficiency*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D003911:Dextrans; D053496:Inositol 1,4,5-Trisphosphate Receptors; C580990:Ip3r2 protein, mouse; D018696:Neuroprotective Agents; C015219:fluorescein isothiocyanate dextran; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium
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