ArticleBritish journal of pharmacology2006
The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling.
Article in British journal of pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 33 citations in OpenAlex.
- Epac1 increases myosin regulatory light-chain phosphorylation, energetic cost of contraction, and susceptibility to heart failure.PloS one · 2025Article
- Alterations in cytoskeletal and CaFrontiers in cardiovascular medicine · 2023Article
- The auxiliary subunit KCNE1 regulates KCNQ1 channel response to sustained calcium-dependent PKC activation.PloS one · 2020Article
- Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic CaJournal of molecular and cellular cardiology · 2019Article
- Thick Filament Protein Network, Functions, and Disease Association.Comprehensive Physiology · 2018Review
- AkrinorFrontiers in pharmacology · 2017Article
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- Apelin increases cardiac contractility via protein kinase Cε- and extracellular signal-regulated kinase-dependent mechanisms.PloS one · 2014Article
- Protein kinase D increases maximal Ca2+-activated tension of cardiomyocyte contraction by phosphorylation of cMyBP-C-Ser315.American journal of physiology. Heart and circulatory physiology · 2012Article
- Myosin light-chain kinase is necessary for membrane homeostasis in cochlear inner hair cells.PloS one · 2012Article
- Heart failure switches the RV alpha1-adrenergic inotropic response from negative to positive.American journal of physiology. Heart and circulatory physiology · 2010Article
- Age-dependent differential crosstalk between alpha(1)-adrenergic and angiotensin receptors.The Canadian journal of cardiology · 2009Article
- Differential contribution of cardiac sarcomeric proteins in the myofibrillar force response to stretch.Pflugers Archiv : European journal of physiology · 2008Article
- Angiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium.Cardiovascular research · 2008Article
- Role of protein kinase C isozymes in the regulation of alpha1-adrenergic receptor-mediated contractions in ovine uterine arteries.Biology of reproduction · 2008Article
- The slow force response to stretch in atrial and ventricular myocardium from human heart: functional relevance and subcellular mechanisms.Progress in biophysics and molecular biologyReview
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study examined the role of myosin light chain kinase (MLCK), PKC isozymes, and inositol 1,4,5-trisphosphate (IP(3)) receptor in the positive inotropic effect of alpha(1)-adrenergic stimulation in atrial myocardium. We measured inotropic effects of phenylephrine (0.3-300 microM) in isolated left atrial preparations (1 Hz, 37 degrees C, 1.8 mM Ca(2+), 0.3 microM nadolol) from male 8-week FVB mice (n=200). Phenylephrine concentration-dependently increased force of contraction from 1.5+/-0.1 to 2.8+/-0.1 mN (mean+/-s.e.m., n=42), which was associated with increased MLC-2a phosphorylation at serine 21 and 22 by 67% and translocation of PKCepsilon but not PKCalpha to membrane (+30%) and myofilament (+50%) fractions.MLCK inhibition using ML-7 or wortmannin right-shifted the concentration-response curve of phenylephrine, reducing its inotropic effect at 10 microM by 73% and 81%, respectively. The compound KIE1-1 (500 nM), an intracellularly acting PKCepsilon translocation inhibitor peptide, prevented PKCepsilon translocation and augmented the maximal inotropic effect of phenylephrine by 40%. In contrast, inhibition of Ca(2+)-dependent PKC translocation (KIC1-1, 500 nM) had no effect. Chelerythrine, a PKC inhibitor, decreased basal force without changing the inotropic effect of phenylephrine. The IP(3) receptor blocker 2-APB (2 and 20 microM) concentration-dependently decreased basal force, but did not affect the concentration-response curve of phenylephrine. These results indicate that activation of MLCK is required for the positive inotropic effect of alpha(1)-adrenergic stimulation, that the Ca(2+)-independent PKCepsilon negatively modulates this effect, and that PKCalpha and IP(3) receptor activation is not involved.
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