Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 385, Issue 3, Pages 408-412Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.05.077
Keywords
Calcium oscillations; Orexin-A; Hypocretin-1; OX1 receptor; Receptor; TRP channel; Phospholipase A(2)
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Funding
- Finnish Ministry of Education
- Academy of Finland
- Sigrid Juselius Foundation
- Northern Savo Regional Fund of the Finnish Cultural Foundation
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Oscillations of intracellular Ca2+ provide a novel mechanism for sustained activation of cellular Processes. Receptor-activated oscillations are mainly thought to occur through rhythmic IP3-dependent store discharge. However, as shown here in HEK293 cells 1 nM orexin-A (Ox-A) acting at OX1 receptors (OX1R) triggered oscillatory Ca2+ responses, requiring external Ca2+. These responses were attenuated by interference with TRPC3 channel (but not TRPC1/4) function using dominant negative constructs, elevated Mg2+ (a blocker of many TRP channels) or inhibition of phospholipase A(2). These treatments did not affect Ca2+ oscillations elicited by high concentrations of Ox-A (100 nM) in the absence of external Ca2+. OX1R are thus able to activate TRPC(3)-channel-dependent oscillatory responses independently of store discharge. (C) 2009 Elsevier Inc. All rights reserved.
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