Abstract
Altered sarcoplasmic reticulum (SR) Ca2+-ATPase and Na +-Ca2+ exchange (NCX) function have been implicated in depressing SR Ca2+ content and contractile function in heart failure (HF). Enhanced diastolic ryanodine receptor (RyR) leak could also lower SR Ca2+ load in HF, but direct cellular measurements are lacking. In this study, we measure SR Ca2+ leak directly in intact isolated rabbit ventricular myocytes from a well-developed nonischemic HF model. Abrupt block of SR Ca2+ leak by tetracaine shifts Ca2+ from the cytosol to SR. The tetracaine-induced decline in [Ca2+]i and increase total SR Ca2+ load ([Ca2+]SRT) directly indicate the SR Ca2+ leak (before tetracaine). Diastolic SR Ca2+ leak increases with [Ca2+]SRT, and for any [Ca2+]SRT is greater in HF versus control. Mathematical modeling was used to compare the relative impact of alterations in SR Ca2+ leak, SR Ca2+-ATPase, and Na+-Ca 2+ exchange on SR Ca2+ load in HF. We conclude that increased diastolic SR Ca2+ leak in HF may contribute to reductions in SR Ca2+ content, but changes in NCX in this HF model have more impact on [Ca2+]SRT.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 592-594 |
| Number of pages | 3 |
| Journal | Circulation Research |
| Volume | 93 |
| Issue number | 7 |
| DOIs | |
| State | Published - Oct 3 2003 |
| Externally published | Yes |
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Keywords
- Ca pump
- Excitation-contraction coupling
- Heart failure
- Ryanodine receptors
- Sarcoplasmic reticulum
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Elevated sarcoplasmic reticulum Ca2+ leak in intact ventricular myocytes from rabbits in heart failure. / Shannon, Thomas R.; Pogwizd, Steven M.; Bers, Donald M.
In: Circulation Research, Vol. 93, No. 7, 03.10.2003, p. 592-594.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Elevated sarcoplasmic reticulum Ca2+ leak in intact ventricular myocytes from rabbits in heart failure
AU - Shannon, Thomas R.
AU - Pogwizd, Steven M.
AU - Bers, Donald M
PY - 2003/10/3
Y1 - 2003/10/3
N2 - Altered sarcoplasmic reticulum (SR) Ca2+-ATPase and Na +-Ca2+ exchange (NCX) function have been implicated in depressing SR Ca2+ content and contractile function in heart failure (HF). Enhanced diastolic ryanodine receptor (RyR) leak could also lower SR Ca2+ load in HF, but direct cellular measurements are lacking. In this study, we measure SR Ca2+ leak directly in intact isolated rabbit ventricular myocytes from a well-developed nonischemic HF model. Abrupt block of SR Ca2+ leak by tetracaine shifts Ca2+ from the cytosol to SR. The tetracaine-induced decline in [Ca2+]i and increase total SR Ca2+ load ([Ca2+]SRT) directly indicate the SR Ca2+ leak (before tetracaine). Diastolic SR Ca2+ leak increases with [Ca2+]SRT, and for any [Ca2+]SRT is greater in HF versus control. Mathematical modeling was used to compare the relative impact of alterations in SR Ca2+ leak, SR Ca2+-ATPase, and Na+-Ca 2+ exchange on SR Ca2+ load in HF. We conclude that increased diastolic SR Ca2+ leak in HF may contribute to reductions in SR Ca2+ content, but changes in NCX in this HF model have more impact on [Ca2+]SRT.
AB - Altered sarcoplasmic reticulum (SR) Ca2+-ATPase and Na +-Ca2+ exchange (NCX) function have been implicated in depressing SR Ca2+ content and contractile function in heart failure (HF). Enhanced diastolic ryanodine receptor (RyR) leak could also lower SR Ca2+ load in HF, but direct cellular measurements are lacking. In this study, we measure SR Ca2+ leak directly in intact isolated rabbit ventricular myocytes from a well-developed nonischemic HF model. Abrupt block of SR Ca2+ leak by tetracaine shifts Ca2+ from the cytosol to SR. The tetracaine-induced decline in [Ca2+]i and increase total SR Ca2+ load ([Ca2+]SRT) directly indicate the SR Ca2+ leak (before tetracaine). Diastolic SR Ca2+ leak increases with [Ca2+]SRT, and for any [Ca2+]SRT is greater in HF versus control. Mathematical modeling was used to compare the relative impact of alterations in SR Ca2+ leak, SR Ca2+-ATPase, and Na+-Ca 2+ exchange on SR Ca2+ load in HF. We conclude that increased diastolic SR Ca2+ leak in HF may contribute to reductions in SR Ca2+ content, but changes in NCX in this HF model have more impact on [Ca2+]SRT.
KW - Ca pump
KW - Excitation-contraction coupling
KW - Heart failure
KW - Ryanodine receptors
KW - Sarcoplasmic reticulum
UR - http://www.scopus.com/inward/record.url?scp=0141752833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141752833&partnerID=8YFLogxK
U2 - 10.1161/01.RES.0000093399.11734.B3
DO - 10.1161/01.RES.0000093399.11734.B3
M3 - Article
C2 - 12946948
AN - SCOPUS:0141752833
VL - 93
SP - 592
EP - 594
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 7
ER -