title: The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy.
abstract: As exceptionally calcium selective store-operated channels, Orai channels play a prominent role in cellular calcium signaling. While most studied in the immune system, we are beginning to recognize that Orai1 provides unique calcium signaling pathways in numerous tissue contexts. To assess the involvement of Orai1 in cardiac hypertrophy we used transverse aortic constriction to model pressure overload cardiac hypertrophy and heart failure in Orai1 deficient mice. We demonstrate that Orai1 deficient mice have significantly decreased survival in this pressure overload model. Transthoracic echocardiography reveals that Orai1 deficient mice develop rapid dilated cardiomyopathy, with greater loss of function, and histological and molecular data indicate that this pathology is associated with significant apoptosis, but not major differences in cellular hypertrophy, fibrosis, and some major hypertrophic makers. Orai1 represents a crucial calcium entry mechanism in the compensation of the heart to pressure overload over-load, and the development of dilated cardiomyopathy.
authors.affiliation: Laboratory of Experimental Medicine; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA; Department of Cell & Molecular Biology; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA.
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Horton
authors.affiliation: Laboratory of Experimental Medicine; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA; Department of Molecular Biosciences & Bioengineering; University of Hawaii; Honolulu, HI USA.
authors.forename: Cadie L
authors.initials: CL
authors.lastname: Buckley
authors.affiliation: Laboratory of Experimental Medicine; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA; Department of Cell & Molecular Biology; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA.
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Alvarez
authors.affiliation: Laboratory of Experimental Medicine; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA; Department of Molecular Biosciences & Bioengineering; University of Hawaii; Honolulu, HI USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Schorlemmer
authors.affiliation: Laboratory of Experimental Medicine; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA; Department of Cell & Molecular Biology; John A. Burns School of Medicine; University of Hawaii; Honolulu, HI USA; Department of Molecular Biosciences & Bioengineering; University of Hawaii; Honolulu, HI USA; Chaminade University; Honolulu, HI USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stokes
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D006332:Cardiomegaly / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071740:ORAI1 Protein
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; D002118:Calcium
keywords: CRACM1; ICRAC; Orai1; apoptosis; contraction coupling; dilated cardiomyopathy; pressure overload