PMID- 26713852
OWN - NLM
STAT- MEDLINE
DCOM- 20160706
LR  - 20220321
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - Cellular Hypertrophy and Increased Susceptibility to Spontaneous Calcium-Release 
      of Rat Left Atrial Myocytes Due to Elevated Afterload.
PG  - e0144309
LID - 10.1371/journal.pone.0144309 [doi]
LID - e0144309
AB  - 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.
FAU - Zhang, Haifei
AU  - Zhang H
AD  - Cardiovascular Research Laboratories, School of Physiology, Pharmacology & 
      Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
FAU - Cannell, Mark B
AU  - Cannell MB
AD  - Cardiovascular Research Laboratories, School of Physiology, Pharmacology & 
      Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
FAU - Kim, Shang Jin
AU  - Kim SJ
AD  - Cardiovascular Research Laboratories, School of Physiology, Pharmacology & 
      Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
FAU - Watson, Judy J
AU  - Watson JJ
AD  - Cardiovascular Research Laboratories, School of Physiology, Pharmacology & 
      Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
FAU - Norman, Ruth
AU  - Norman R
AD  - School of Biomedical Sciences, Garstang, University of Leeds, Leeds, LS2 9JT, 
      United Kingdom.
FAU - Calaghan, Sarah C
AU  - Calaghan SC
AD  - School of Biomedical Sciences, Garstang, University of Leeds, Leeds, LS2 9JT, 
      United Kingdom.
FAU - Orchard, Clive H
AU  - Orchard CH
AD  - Cardiovascular Research Laboratories, School of Physiology, Pharmacology & 
      Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
FAU - James, Andrew F
AU  - James AF
AD  - Cardiovascular Research Laboratories, School of Physiology, Pharmacology & 
      Neuroscience, University of Bristol, Bristol, BS8 1TD, United Kingdom.
LA  - eng
GR  - RG/12/10/29802/BHF_/British Heart Foundation/United Kingdom
GR  - RG/12/10 CHO AFJ MBC/British Heart Foundation/United Kingdom
GR  - PG/07/101 AFJ CHO/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151229
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
SB  - IM
MH  - Animals
MH  - Atrial Fibrillation/*physiopathology
MH  - Calcium Signaling
MH  - Cell Enlargement
MH  - Cells, Cultured
MH  - Heart Atria/*pathology/physiopathology
MH  - Hypertrophy
MH  - Male
MH  - Myocytes, Cardiac/*physiology
MH  - Rats, Wistar
MH  - Ryanodine Receptor Calcium Release Channel/metabolism
PMC - PMC4694654
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/12/30 06:00
MHDA- 2016/07/07 06:00
PMCR- 2015/12/29
CRDT- 2015/12/30 06:00
PHST- 2015/05/27 00:00 [received]
PHST- 2015/11/16 00:00 [accepted]
PHST- 2015/12/30 06:00 [entrez]
PHST- 2015/12/30 06:00 [pubmed]
PHST- 2016/07/07 06:00 [medline]
PHST- 2015/12/29 00:00 [pmc-release]
AID - PONE-D-15-22913 [pii]
AID - 10.1371/journal.pone.0144309 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 29;10(12):e0144309. doi: 10.1371/journal.pone.0144309. 
      eCollection 2015.