Publications

BibTex format

@article{Rowlands:2017:10.1152/ajpheart.00244.2017,
author = {Rowlands, C and Owen, T and Lawal, S and Cao, S and Pandey, S and Yang, H-Y and Song, W and Wilkinson, R and Alvarez-Laviada, A and Gehmlich, K and Marston, S and MacLeod, KT},
doi = {10.1152/ajpheart.00244.2017},
journal = {American Journal of Physiology: Heart and Circulatory Physiology},
pages = {H1213--H1226},
title = {Age and strain related aberrant Ca2+ release is associated with sudden cardiac death in the ACTC E99K mouse model of hypertrophic cardiomyopathy},
url = {http://dx.doi.org/10.1152/ajpheart.00244.2017},
volume = {313},
year = {2017}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Patients with hypertrophic cardiomyopathy, particularly young adults, can die from arrhythmia, but the mechanism underlying abnormal rhythm formation remains unknown. C57Bl6 × CBA/Ca mice carrying a cardiac actin (ACTC) E99K (Glu99Lys) mutation reproduce many aspects of human hypertrophic cardiomyopathy, including increased myofilament Ca2+ sensitivity and sudden death in a proportion (up to 40%) of young (28−40 day old) animals. We studied the hearts of transgenic (TG; ACTC E99K) mice and their non-TG (NTG) littermates when they were in their vulnerable period (28–40 days old) and when they were adult (8–12 wk old). Ventricular myocytes were isolated from the hearts of TG and NTG mice at these two time points. We also examined the hearts of mice that died suddenly (SCD). SCD animals had approximately four times more collagen compared with age-matched NTG mice, yet myocyte cell size was normal. Young TG mice had double the collagen content of NTG mice. Contraction and Ca2+ transients were greater in cells from young TG mice compared with their NTG littermates but not in cells from adult mice (TG or NTG). Cells from young TG mice had a greater propensity for Ca2+ waves than NTG littermates, and, despite similar sarcoplasmic reticulum Ca2+ content, a proportion of these cells had larger Ca2+ spark mass. We found that the probability of SCD in young TG mice was increased when the mutation was expressed in animals with a CBA/Ca2+ background and almost eliminated in mice bred on a C57Bl6 background. The latter TG mice had normal cellular Ca2+ homeostasis.
AU  - Rowlands,C
AU  - Owen,T
AU  - Lawal,S
AU  - Cao,S
AU  - Pandey,S
AU  - Yang,H-Y
AU  - Song,W
AU  - Wilkinson,R
AU  - Alvarez-Laviada,A
AU  - Gehmlich,K
AU  - Marston,S
AU  - MacLeod,KT
DO  - 10.1152/ajpheart.00244.2017
EP  - 1226
PY  - 2017///
SN  - 1522-1539
SP  - 1213
TI  - Age and strain related aberrant Ca2+ release is associated with sudden cardiac death in the ACTC E99K mouse model of hypertrophic cardiomyopathy
T2  - American Journal of Physiology: Heart and Circulatory Physiology
UR  - http://dx.doi.org/10.1152/ajpheart.00244.2017
UR  - http://hdl.handle.net/10044/1/51314
VL  - 313
ER  -

Download

ProfessorSteveMarston

Contact

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)