@article{fdi:010066150,
  title = {{R}econciling depressed {C}a2+ sparks occurrence with enhanced {R}y{R}2 activity in failing mice cardiomyocytes},
  author = {{R}uiz-{H}urtado, {G}. and {L}i, {L}. {W}. and {F}ernandez-{V}elasco, {M}. and {R}ueda, {A}. and {L}efebvre, {F}. and {W}ang, {Y}. {Y}. and {M}ateo, {P}. and {C}assan, {C}{\'e}cile and {G}ellen, {B}. and {B}enitah, {J}. {P}. and {G}omez, {A}. {M}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A}bnormalities in cardiomyocyte {C}a2+ handling contribute to impaired contractile function in heart failure ({HF}). {E}xperiments on single ryanodine receptors ({R}y{R}s) incorporated into lipid bilayers have indicated that {R}y{R}s from failing hearts are more active than those from healthy hearts. {H}ere, we analyzed spontaneous {C}a2+ sparks (brief, localized increased in [{C}a2+](i)) to evaluate {R}y{R} cluster activity in situ in a mouse post-myocardial infarction ({PMI}) model of {HF}. {T}he cardiac ejection fraction of {PMI} mice was reduced to. 30% of that of sham-operated (sham) mice, and their cardiomyocytes were hypertrophied. {T}he [{C}a2+](i) transient amplitude and sarcoplasmic reticulum ({SR}) {C}a2+ load were decreased in intact {PMI} cardiomyocytes compared with those from sham mice, and spontaneous {C}a2+ sparks were less frequent, whereas the fractional release and the frequency of {C}a2+ waves were both increased, suggesting higher {R}y{R} activity. {I}n permeabilized cardiomyocytes, in which the internal solution can be controlled, {C}a2+ sparks were more frequent in {PMI} cells (under conditions of similar {SR} {C}a2+ load), confirming the enhanced {R}y{R} activity. {H}owever, in intact cells from {PMI} mice, the {C}a2+ sparks frequency normalized by the {SR} {C}a2+ load in that cell were reduced compared with those in sham mice, indicating that the cytosolic environment in intact cells contributes to the decrease in {C}a2+ spark frequency. {I}ndeed, using an internal "failing solution" with less {ATP} (as found in {HF}), we observed a dramatic decrease in {C}a2+ spark frequency in permeabilized {PMI} and sham myocytes. {I}n conclusion, our data show that, even if isolated {R}y{R} channels show more activity in {HF}, concomitant alterations in intracellular media composition and {SR} {C}a2+ load may mask these effects at the {C}a2+ spark level in intact cells. {N}onetheless, in this scenario, the probability of arrhythmogenic {C}a2+ waves is enhanced, and they play a potential role in the increase in arrhythmia events in {HF} patients.},
  keywords = {},
  booktitle = {},
  journal = {{J}ournal of {G}eneral {P}hysiology},
  volume = {146},
  numero = {4},
  pages = {295--306},
  ISSN = {0022-1295},
  year = {2015},
  DOI = {10.1085/jgp.201511366},
  URL = {https://www.documentation.ird.fr/hor/fdi:010066150},
}