title: Cytosolic and nuclear calcium signaling in atrial myocytes: IP3-mediated calcium release and the role of mitochondria.
abstract: In rabbit atrial myocytes Ca signaling has unique features due to the lack of transverse (t) tubules, the spatial arrangement of mitochondria and the contribution of inositol-1,4,5-trisphosphate (IP3) receptor-induced Ca release (IICR). During excitation-contraction coupling action potential-induced elevation of cytosolic [Ca] originates in the cell periphery from Ca released from the junctional sarcoplasmic reticulum (j-SR) and then propagates by Ca-induced Ca release from non-junctional (nj-) SR toward the cell center. The subsarcolemmal region between j-SR and the first array of nj-SR Ca release sites is devoid of mitochondria which results in a rapid propagation of activation through this domain, whereas the subsequent propagation through the nj-SR network occurs at a velocity typical for a propagating Ca wave. Inhibition of mitochondrial Ca uptake with the Ca uniporter blocker Ru360 accelerates propagation and increases the amplitude of Ca transients (CaTs) originating from nj-SR. Elevation of cytosolic IP3 levels by rapid photolysis of caged IP3 has profound effects on the magnitude of subcellular CaTs with increased Ca release from nj-SR and enhanced CaTs in the nuclear compartment. IP3 uncaging restricted to the nucleus elicites 'mini'-Ca waves that remain confined to this compartment. Elementary IICR events (Ca puffs) preferentially originate in the nucleus in close physical association with membrane structures of the nuclear envelope and the nucleoplasmic reticulum. The data suggest that in atrial myocytes the nucleus is an autonomous Ca signaling domain where Ca dynamics are primarily governed by IICR.
authors.affiliation: a Department of Molecular Biophysics and Physiology ; Rush University Medical Center ; Chicago , IL USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Hohendanner
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Maxwell
authors.forename: Lothar A
authors.initials: LA
authors.lastname: Blatter
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D003600:Cytosol / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D011817:Rabbits
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D002118:Calcium
keywords: 2-APB, 2-aminoethoxydiphenyl borate; AP, action potential; CICR, Ca-induced Ca release; CRU, Ca release units; CT, central; CaT, Ca transient; ECC, excitation-contraction coupling; IICR; IICR, IP3R-induced Ca release; IP3; IP3R, Inositol-1,4,5-trisphosphate receptor; LCC, L-type Ca channels; MCU, mitochondrial Ca uniporter; NE, nuclear envelope; NFAT, nuclear factor of activated T cells; NPR, nucleoplasmic reticulum; RyR, ryanodine receptor; SR, sarcoplasmic reticulum; SS, subsarcolemmal; TF50, time to half-maximal amplitude; TZ, transition zone.; [Ca]i, cytosolic Ca concentration; [Ca]mito, mitochondrial Ca concentration; atria; excitation-contraction coupling; j-SR, junctional SR; mitochondria; nj-SR, non-junctional SR; nuclear calcium; t-tubule, transverse tubule