| First Author | Puglisi JL | Year | 2014 |
| Journal | Arch Biochem Biophys | Volume | 552-553 |
| Pages | 50-9 | PubMed ID | 24480308 |
| Mgi Jnum | J:227878 | Mgi Id | MGI:5703707 |
| Doi | 10.1016/j.abb.2014.01.019 | Citation | Puglisi JL, et al. (2014) Influence of a constitutive increase in myofilament Ca(2+)-sensitivity on Ca(2+)-fluxes and contraction of mouse heart ventricular myocytes. Arch Biochem Biophys 552-553:50-9 |
| abstractText | Chronic increases in myofilament Ca(2+)-sensitivity in the heart are known to alter gene expression potentially modifying Ca(2+)-homeostasis and inducing arrhythmias. We tested age-dependent effects of a chronic increase in myofilament Ca(2+)-sensitivity on induction of altered alter gene expression and activity of Ca(2+) transport systems in cardiac myocytes. Our approach was to determine the relative contributions of the major mechanisms responsible for restoring Ca(2+) to basal levels in field stimulated ventricular myocytes. Comparisons were made from ventricular myocytes isolated from non-transgenic (NTG) controls and transgenic mice expressing the fetal, slow skeletal troponin I (TG-ssTnI) in place of cardiac TnI (cTnI). Replacement of cTnI by ssTnI induces an increase in myofilament Ca(2+)-sensitivity. Comparisons included myocytes from relatively young (5-7months) and older mice (11-13months). Employing application of caffeine in normal Tyrode and in 0Na(+) 0Ca(2+) solution, we were able to dissect the contribution of the sarcoplasmic reticulum Ca(2+) pump (SR Ca(2+)-ATPase), the Na(+)/Ca(2+) exchanger (NCX), and "slow mechanisms" representing the activity of the sarcolemmal Ca(2+) pump and the mitochondrial Ca(2+) uniporter. The relative contribution of the SR Ca(2+)-ATPase to restoration of basal Ca(2+) levels in younger TG-ssTnI myocytes was lower than in NTG (81.12+/-2.8% vs 92.70+/-1.02%), but the same in the older myocytes. Younger and older NTG myocytes demonstrated similar contributions from the SR Ca(2+)-ATPase and NCX to restoration of basal Ca(2+). However, the slow mechanisms for Ca(2+) removal were increased in the older NTG (3.4+/-0.3%) vs the younger NTG myocytes (1.4+/-0.1%). Compared to NTG, younger TG-ssTnI myocytes demonstrated a significantly bigger contribution of the NCX (16+/-2.7% in TG vs 6.9+/-0.9% in NTG) and slow mechanisms (3.3+/-0.4% in TG vs 1.4+/-0.1% in NTG). In older TG-ssTnI myocytes the contributions were not significantly different from NTG (NCX: 4.9+/-0.6% in TG vs 5.5+/-0.7% in NTG; slow mechanisms: 2.5+/-0.3% in TG vs 3.4+/-0.3% in NTG). Our data indicate that constitutive increases in myofilament Ca(2+)-sensitivity alter the relative significance of the NCX transport system involved in Ca(2+)-homeostasis only in a younger group of mice. This modification may be of significance in early changes in altered gene expression and electrical stability hearts with increased myofilament Ca-sensitivity. |
