title: Cellular Hypertrophy and Increased Susceptibility to Spontaneous Calcium-Release of Rat Left Atrial Myocytes Due to Elevated Afterload.
abstract: Atrial remodeling due to elevated arterial pressure predisposes the heart to atrial fibrillation (AF). Although abnormal sarcoplasmic reticulum (SR) function has been associated with AF, there is little information on the effects of elevated afterload on atrial Ca2+-handling. We investigated the effects of ascending aortic banding (AoB) on Ca2+-handling in rat isolated atrial myocytes in comparison to age-matched sham-operated animals (Sham). Myocytes were either labelled for ryanodine receptor (RyR) or loaded with fluo-3-AM and imaged by confocal microscopy. AoB myocytes were hypertrophied in comparison to Sham controls (P<0.0001). RyR labeling was localized to the z-lines and to the cell edge. There were no differences between AoB and Sham in the intensity or pattern of RyR-staining. In both AoB and Sham, electrical stimulation evoked robust SR Ca2+-release at the cell edge whereas Ca2+ transients at the cell center were much smaller. Western blotting showed a decreased L-type Ca channel expression but no significant changes in RyR or RyR phosphorylation or in expression of Na+/Ca2+ exchanger, SR Ca2+ ATPase or phospholamban. Mathematical modeling indicated that [Ca2+]i transients at the cell center were accounted for by simple centripetal diffusion of Ca2+ released at the cell edge. In contrast, caffeine (10 mM) induced Ca2+ release was uniform across the cell. The caffeine-induced transient was smaller in AoB than in Sham, suggesting a reduced SR Ca2+-load in hypertrophied cells. There were no significant differences between AoB and Sham cells in the rate of Ca2+ extrusion during recovery of electrically-stimulated or caffeine-induced transients. The incidence and frequency of spontaneous Ca2+-transients following rapid-pacing (4 Hz) was greater in AoB than in Sham myocytes. In conclusion, elevated afterload causes cellular hypertrophy and remodeling of atrial SR Ca2+-release.
authors.affiliation: Cardiovascular Research Laboratories, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Haifei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cardiovascular Research Laboratories, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Cannell
authors.affiliation: Cardiovascular Research Laboratories, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Shang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Cardiovascular Research Laboratories, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Judy J
authors.initials: JJ
authors.lastname: Watson
authors.affiliation: School of Biomedical Sciences, Garstang, University of Leeds, Leeds, LS2 9JT, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Norman
authors.affiliation: School of Biomedical Sciences, Garstang, University of Leeds, Leeds, LS2 9JT, United Kingdom.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Calaghan
authors.affiliation: Cardiovascular Research Laboratories, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Clive H
authors.initials: CH
authors.lastname: Orchard
authors.affiliation: Cardiovascular Research Laboratories, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: James
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D020013:Calcium Signaling; D049108:Cell Enlargement; D002478:Cells, Cultured; D006325:Heart Atria / Q000473:pathology* / Q000503:physiopathology; D006984:Hypertrophy; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology*; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel