Abstract
Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca 2+ release from Ryanodine Receptors (RyRs). We investigated whether this deficit can be traced to nanoscale RyR reorganization. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters. Functional groupings of RyR clusters which produce Ca 2+ sparks (Ca 2+ release units, CRUs) also became less solid. An increased fraction of small CRUs in HF was linked to augmented ‘silent’ Ca 2+ leak, not visible as sparks. Larger multi-cluster CRUs common in HF also exhibited low fidelity spark generation. When successfully triggered, sparks in failing cells displayed slow kinetics as Ca 2+ spread across dispersed CRUs. During the action potential, these slow sparks protracted and desynchronized the overall Ca 2+ transient. Thus, nanoscale RyR reorganization during HF augments Ca 2+ leak and slows Ca 2+ release kinetics, leading to weakened contraction in this disease.
| Original language | English (US) |
|---|---|
| Article number | e39427 |
| Journal | eLife |
| Volume | 7 |
| DOIs | |
| State | Published - Oct 2018 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
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Ryanodine receptor dispersion disrupts Ca 2+ release in failing cardiac myocytes . / Kolstad, Terje R.; van den Brink, Jonas; Macquaide, Niall; Lunde, Per Kristian; Frisk, Michael; Aronsen, Jan Magnus; Norden, Einar S.; Cataliotti, Alessandro; Sjaastad, Ivar; Sejersted, Ole M.; Edwards, Andrew G.; Lines, Glenn Terje; Louch, William E.
In: eLife, Vol. 7, e39427, 10.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ryanodine receptor dispersion disrupts Ca 2+ release in failing cardiac myocytes
AU - Kolstad, Terje R.
AU - van den Brink, Jonas
AU - Macquaide, Niall
AU - Lunde, Per Kristian
AU - Frisk, Michael
AU - Aronsen, Jan Magnus
AU - Norden, Einar S.
AU - Cataliotti, Alessandro
AU - Sjaastad, Ivar
AU - Sejersted, Ole M.
AU - Edwards, Andrew G.
AU - Lines, Glenn Terje
AU - Louch, William E.
PY - 2018/10
Y1 - 2018/10
N2 - Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca 2+ release from Ryanodine Receptors (RyRs). We investigated whether this deficit can be traced to nanoscale RyR reorganization. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters. Functional groupings of RyR clusters which produce Ca 2+ sparks (Ca 2+ release units, CRUs) also became less solid. An increased fraction of small CRUs in HF was linked to augmented ‘silent’ Ca 2+ leak, not visible as sparks. Larger multi-cluster CRUs common in HF also exhibited low fidelity spark generation. When successfully triggered, sparks in failing cells displayed slow kinetics as Ca 2+ spread across dispersed CRUs. During the action potential, these slow sparks protracted and desynchronized the overall Ca 2+ transient. Thus, nanoscale RyR reorganization during HF augments Ca 2+ leak and slows Ca 2+ release kinetics, leading to weakened contraction in this disease.
AB - Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca 2+ release from Ryanodine Receptors (RyRs). We investigated whether this deficit can be traced to nanoscale RyR reorganization. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters. Functional groupings of RyR clusters which produce Ca 2+ sparks (Ca 2+ release units, CRUs) also became less solid. An increased fraction of small CRUs in HF was linked to augmented ‘silent’ Ca 2+ leak, not visible as sparks. Larger multi-cluster CRUs common in HF also exhibited low fidelity spark generation. When successfully triggered, sparks in failing cells displayed slow kinetics as Ca 2+ spread across dispersed CRUs. During the action potential, these slow sparks protracted and desynchronized the overall Ca 2+ transient. Thus, nanoscale RyR reorganization during HF augments Ca 2+ leak and slows Ca 2+ release kinetics, leading to weakened contraction in this disease.
UR - http://www.scopus.com/inward/record.url?scp=85056712349&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056712349&partnerID=8YFLogxK
U2 - 10.7554/eLife.39427
DO - 10.7554/eLife.39427
M3 - Article
C2 - 30375974
AN - SCOPUS:85056712349
VL - 7
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e39427
ER -