Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis.
The creatine kinase (CK) system is involved in the rapid transport of high-energy phosphates from the mitochondria to the sites of maximal energy requirements such as myofibrils and sarcolemmal ion pumps. Hearts of mice with a combined knockout of cytosolic M-CK and mitochondrial CK (M/Mito-CK(-/-))...
| Asıl Yazarlar: | , , , , , , |
|---|---|
| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
2004
|
| _version_ | 1826292632394924032 |
|---|---|
| author | Spindler, M Meyer, K Strömer, H Leupold, A Boehm, E Wagner, H Neubauer, S |
| author_facet | Spindler, M Meyer, K Strömer, H Leupold, A Boehm, E Wagner, H Neubauer, S |
| author_sort | Spindler, M |
| collection | OXFORD |
| description | The creatine kinase (CK) system is involved in the rapid transport of high-energy phosphates from the mitochondria to the sites of maximal energy requirements such as myofibrils and sarcolemmal ion pumps. Hearts of mice with a combined knockout of cytosolic M-CK and mitochondrial CK (M/Mito-CK(-/-)) show unchanged basal left ventricular (LV) performance but reduced myocardial high-energy phosphate concentrations. Moreover, skeletal muscle from M/Mito-CK(-/-) mice demonstrates altered Ca2+ homeostasis. Our hypothesis was that in CK-deficient hearts, a cardiac phenotype can be unmasked during acute stress conditions and that susceptibility to ischemia-reperfusion injury is increased because of altered Ca2+ homeostasis. We simultaneously studied LV performance and myocardial Ca2+ metabolism in isolated, perfused hearts of M/Mito-CK(-/-) (n = 6) and wild-type (WT, n = 8) mice during baseline, 20 min of no-flow ischemia, and recovery. Whereas LV performance was not different during baseline conditions, LV contracture during ischemia developed significantly earlier (408 +/- 72 vs. 678 +/- 54 s) and to a greater extent (50 +/- 2 vs. 36 +/- 3 mmHg) in M/Mito-CK(-/-) mice. During reperfusion, recovery of diastolic function was impaired (LV end-diastolic pressure: 22 +/- 3 vs. 10 +/- 2 mmHg), whereas recovery of systolic performance was delayed, in M/Mito-CK(-/-) mice. In parallel, Ca2+ transients were similar during baseline conditions; however, M/Mito-CK(-/-) mice showed a greater increase in diastolic Ca2+ concentration ([Ca2+]) during ischemia (237 +/- 54% vs. 167 +/- 25% of basal [Ca2+]) compared with WT mice. In conclusion, CK-deficient hearts show an increased susceptibility of LV performance and Ca2+ homeostasis to ischemic injury, associated with a blunted postischemic recovery. This demonstrates a key function of an intact CK system for maintenance of Ca2+ homeostasis and LV mechanics under metabolic stress conditions. |
| first_indexed | 2024-03-07T03:17:41Z |
| format | Journal article |
| id | oxford-uuid:b65ac823-4cb1-45b8-a77f-82640e014b0c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:17:41Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:b65ac823-4cb1-45b8-a77f-82640e014b0c2022-03-27T04:40:21ZCreatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b65ac823-4cb1-45b8-a77f-82640e014b0cEnglishSymplectic Elements at Oxford2004Spindler, MMeyer, KStrömer, HLeupold, ABoehm, EWagner, HNeubauer, SThe creatine kinase (CK) system is involved in the rapid transport of high-energy phosphates from the mitochondria to the sites of maximal energy requirements such as myofibrils and sarcolemmal ion pumps. Hearts of mice with a combined knockout of cytosolic M-CK and mitochondrial CK (M/Mito-CK(-/-)) show unchanged basal left ventricular (LV) performance but reduced myocardial high-energy phosphate concentrations. Moreover, skeletal muscle from M/Mito-CK(-/-) mice demonstrates altered Ca2+ homeostasis. Our hypothesis was that in CK-deficient hearts, a cardiac phenotype can be unmasked during acute stress conditions and that susceptibility to ischemia-reperfusion injury is increased because of altered Ca2+ homeostasis. We simultaneously studied LV performance and myocardial Ca2+ metabolism in isolated, perfused hearts of M/Mito-CK(-/-) (n = 6) and wild-type (WT, n = 8) mice during baseline, 20 min of no-flow ischemia, and recovery. Whereas LV performance was not different during baseline conditions, LV contracture during ischemia developed significantly earlier (408 +/- 72 vs. 678 +/- 54 s) and to a greater extent (50 +/- 2 vs. 36 +/- 3 mmHg) in M/Mito-CK(-/-) mice. During reperfusion, recovery of diastolic function was impaired (LV end-diastolic pressure: 22 +/- 3 vs. 10 +/- 2 mmHg), whereas recovery of systolic performance was delayed, in M/Mito-CK(-/-) mice. In parallel, Ca2+ transients were similar during baseline conditions; however, M/Mito-CK(-/-) mice showed a greater increase in diastolic Ca2+ concentration ([Ca2+]) during ischemia (237 +/- 54% vs. 167 +/- 25% of basal [Ca2+]) compared with WT mice. In conclusion, CK-deficient hearts show an increased susceptibility of LV performance and Ca2+ homeostasis to ischemic injury, associated with a blunted postischemic recovery. This demonstrates a key function of an intact CK system for maintenance of Ca2+ homeostasis and LV mechanics under metabolic stress conditions. |
| spellingShingle | Spindler, M Meyer, K Strömer, H Leupold, A Boehm, E Wagner, H Neubauer, S Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. |
| title | Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. |
| title_full | Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. |
| title_fullStr | Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. |
| title_full_unstemmed | Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. |
| title_short | Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. |
| title_sort | creatine kinase deficient hearts exhibit increased susceptibility to ischemia reperfusion injury and impaired calcium homeostasis |
| work_keys_str_mv | AT spindlerm creatinekinasedeficientheartsexhibitincreasedsusceptibilitytoischemiareperfusioninjuryandimpairedcalciumhomeostasis AT meyerk creatinekinasedeficientheartsexhibitincreasedsusceptibilitytoischemiareperfusioninjuryandimpairedcalciumhomeostasis AT stromerh creatinekinasedeficientheartsexhibitincreasedsusceptibilitytoischemiareperfusioninjuryandimpairedcalciumhomeostasis AT leupolda creatinekinasedeficientheartsexhibitincreasedsusceptibilitytoischemiareperfusioninjuryandimpairedcalciumhomeostasis AT boehme creatinekinasedeficientheartsexhibitincreasedsusceptibilitytoischemiareperfusioninjuryandimpairedcalciumhomeostasis AT wagnerh creatinekinasedeficientheartsexhibitincreasedsusceptibilitytoischemiareperfusioninjuryandimpairedcalciumhomeostasis AT neubauers creatinekinasedeficientheartsexhibitincreasedsusceptibilitytoischemiareperfusioninjuryandimpairedcalciumhomeostasis |