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Reduced contractile response to α1-adrenergic stimulation in atria from mice with chronic cardiac calmodulin kinase II inhibition
- Source :
-
Journal of Molecular & Cellular Cardiology . Mar2007, Vol. 42 Issue 3, p643-652. 10p. - Publication Year :
- 2007
-
Abstract
- Abstract: The sustained positive inotropic effect of α-adrenoceptor agonists in the heart is associated with a small increase in intracellular Ca2+ transients together with a larger sensitization of myofilaments to Ca2+. The multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) could contribute to this effect, either by affecting the Ca2+ release (ryanodine receptor) or by an uptake mechanism (via phospholamban [PLB] and SR Ca2+ ATPase). Here we examined the role of CaMKII in the positive inotropic effect of the α-adrenoceptor agonist phenylephrine in left atria isolated from a genetic mouse model of cardiac CaMKII inhibition (AC3-I). Compared to atria from wild-type (WT) or AC3-C (scrambled peptide), AC3-I atria showed the following abnormalities. PLB phosphorylation at Thr17, a known CaMKII target, was significantly lower (∼20%). Post-rest (30 s, 1 Hz, 37 °C) potentiation of force was absent (AC3-C, 190% of pre-rest amplitude). Basal force was ∼20% lower at 1.8 mM Ca2+, but normal at high Ca2+ concentration (>4.5 mM). The maximal positive inotropic effect of phenylephrine, which was more pronounced at low frequencies in WT and AC3-C atria, lost its frequency dependence (1 Hz to 8 Hz). Thus, the effect of phenylephrine was reduced by ∼50% at 1 Hz, but was normal at 8 Hz. All three groups showed a negative force–frequency relation, and did not differ in the frequency-dependent acceleration of relaxation. Our data indicate a role of CaMKII in post-rest potentiation and the positive inotropic effect of α-adrenergic stimulation at low frequencies. [Copyright &y& Elsevier]
- Subjects :
- *PROTEIN kinases
*RYANODINE
*PHOSPHORYLATION
*CYCLIN-dependent kinases
Subjects
Details
- Language :
- English
- ISSN :
- 00222828
- Volume :
- 42
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular & Cellular Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 24298457
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2006.12.010