Dissociation between contraction and relaxation: The possible role of phospholamban phosphorylation

1987 ◽  
Vol 82 (6) ◽  
pp. 507-516 ◽  
Author(s):  
C. Mundiña Weilenmann ◽  
L. Vittone ◽  
G. Cingolani ◽  
A. Mattiazzi
2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Wen Zhao ◽  
Xiaojing Shi ◽  
Wenjuan Zhou ◽  
Huimin Wang ◽  
Xuepeng Geng ◽  
...  

Peroxiredoxin II (prxII), a cytosolic form of the anti-oxidant peroxiredoxin family, was recently found to be decreased in failing human hearts. Interestingly, in hyperdynamic hearts of two genetically modified mouse models with: a) phospholamban ablation; and b) overexpression of the active inhibitor-1 of protein phosphatase 1, the levels of this cellular peroxidase (prxII) were markedly increased. Acute overexpression of prxII by adenoviral-delivery in adult rat cardiomyocytes (Ad-prxII) was associated with decreases in the basal rates of contraction and relaxation, as well as calcium kinetics. Accordingly, Ad-prxII-AS infected cardiomyocytes exhibited enhanced contractile parameters and Ca-kinetics. The depressed or increased contractility by Ad-prxII or Ad-prxII-AS was associated with parallel decreases or increases in phosphorylation of phospholamban (Ser16 and Thr17). To determine the in vivo effects of prxII on cardiac contractility, three transgenic lines (TG) with 2-3 fold cardiac-specific overexpression of prxII were generated and their cardiac morphologic and functional phenotypes were characterized. The TG mice exhibited no alterations in cardiac pathology or morphology up to 4 months of age. However, langendorf perfusions revealed that cardiac contractility, including the rates of contraction and relaxation (±dp/dtmax) as well as the left ventricular end systolic pressure (LVESP), were significantly depressed in TG mice (to 75, 76 and 63%, respectively), compared to WTs (100%). The depressed function was not associated with any alterations in the expression levels of key SR calcium handling proteins: SERCA2, total phospholamban, calsequestrin and ryanodine receptor. However, the levels of the phosphorylated PLN at Ser16 were found to be reduced to 50% in the TG mice, compared to WTs. These findings indicate that prxII, an anti-oxidant protein, may regulate basal cardiac contractile performance in vivo through phospholamban phosphorylation.


1993 ◽  
Vol 124 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Leticia Vittone ◽  
Cecilia Mundi�a ◽  
Gladys Chiappe de Cingolani ◽  
Alicia Mattiazzi

2020 ◽  
Vol 21 (13) ◽  
pp. 4698 ◽  
Author(s):  
María F. Rozas-Villanueva ◽  
Paola Casanello ◽  
Mauricio A. Retamal

Preeclampsia is a pregnancy complication that appears after 20 weeks of gestation and is characterized by hypertension and proteinuria, affecting both mother and offspring. The cellular and molecular mechanisms that cause the development of preeclampsia are poorly understood. An important feature of preeclampsia is an increase in oxygen and nitrogen derived free radicals (reactive oxygen species/reactive nitrogen species (ROS/RNS), which seem to be central players setting the development and progression of preeclampsia. Cell-to-cell communication may be disrupted as well. Connexins (Cxs), a family of transmembrane proteins that form hemichannels and gap junction channels (GJCs), are essential in paracrine and autocrine cell communication, allowing the movement of signaling molecules between cells as well as between the cytoplasm and the extracellular media. GJCs and hemichannels are fundamental for communication between endothelial and smooth muscle cells and, therefore, in the control of vascular contraction and relaxation. In systemic vasculature, the activity of GJCs and hemichannels is modulated by ROS and RNS. Cxs participate in the development of the placenta and are expressed in placental vasculature. However, it is unknown whether Cxs are modulated by ROS/RNS in the placenta, or whether this potential modulation contributes to the pathogenesis of preeclampsia. Our review addresses the possible role of Cxs in preeclampsia, and the plausible modulation of Cxs-formed channels by ROS and RNS. We suggest these factors may contribute to the development of preeclampsia.


1984 ◽  
Vol 247 (5) ◽  
pp. C424-C432 ◽  
Author(s):  
F. Savabi ◽  
P. J. Geiger ◽  
S. P. Bessman

Isometric contraction and relaxation of glycerinated rabbit psoas muscle fibers containing native creatine kinase (CK) and ATPase activities were studied. Energy for contraction and relaxation was provided either by ADP + creatine phosphate (CP) or ATP alone, and the effectiveness of these additions on rate and maximum force of contraction and relaxation were compared. In the presence of 250 microM ADP, physiological concentration of CP (10 mM) produced faster and stronger contraction and faster and more complete relaxation than equimolar or even higher concentrations of ATP. When contraction was initiated by addition of ADP to fibers preincubated with 10 mM CP, the apparent Km for ADP was 1.18 +/- 0.24 mM. If the fibers were preincubated with ADP and contraction initiated by addition of 10 mM CP, the apparent Km for ADP was more than an order of magnitude smaller (76.0 +/- 4 microM). The observed Km for ADP for contraction was about half the Km for CP in solution (151.5 microM). The apparent Km for CP for rate of contraction was 2.67 +/- .046 mM independent of sequence of addition of ADP. Since these experiments were done in the presence of P1,P5-diadenosine 5'-pentaphosphate, a powerful inhibitor of adenylate kinase, the role of this enzyme in the process was not significant. These observations support the idea of compartmentation of myofibrillar CK in close function with myosin ATPase as part of the phosphoryl creatine energy shuttle.


2012 ◽  
Vol 50 (1) ◽  
pp. 11-20 ◽  
Author(s):  
M.Y. Kochukov ◽  
A. Balasubramanian ◽  
R.C. Noel ◽  
S.P. Marrelli

2006 ◽  
Vol 291 (3) ◽  
pp. H1226-H1235 ◽  
Author(s):  
Hui Dong ◽  
Yanfen Jiang ◽  
Chris R. Triggle ◽  
Xiaofang Li ◽  
Jonathan Lytton

Cytoplasmic free Ca2+ ([Ca2+]cyt) is essential for the contraction and relaxation of blood vessels. The role of plasma membrane Na+/Ca2+ exchange (NCX) activity in the regulation of vascular Ca2+ homeostasis was previously ascribed to the NCX1 protein. However, recent studies suggest that a relatively newly discovered K+-dependent Na+/Ca2+ exchanger, NCKX (gene family SLC24), is also present in vascular smooth muscle. The purpose of the present study was to identify the expression and function of NCKX in arteries. mRNA encoding NCKX3 and NCKX4 was demonstrated by RT-PCR and Northern blot in both rat mesenteric and aortic smooth muscle. NCXK3 and NCKX4 proteins were also demonstrated by immunoblot and immunofluorescence. After voltage-gated Ca2+ channels, store-operated Ca2+ channels, and Na+ pump were pharmacologically blocked, when the extracellular Na+ was replaced with Li+ (0 Na+) to induce reverse mode (Ca2+ entry) activity of Na+/Ca2+ exchangers, a large increase in [Ca2+]cyt signal was observed in primary cultured aortic smooth muscle cells. About one-half of this [Ca2+]cyt signal depended on the extracellular K+. In addition, after the activity of NCX was inhibited by KB-R7943, Na+ replacement-induced Ca2+ entry was absolutely dependent on extracellular K+. In arterial rings denuded of endothelium, a significant fraction of the phenylephrine-induced and nifedipine-resistant aortic or mesenteric contraction could be prevented by removal of extracellular K+. Taken together, these data provide strong evidence for the expression of NCKX proteins in the vascular smooth muscle and their novel role in mediating agonist-stimulated [Ca2+]cyt and thereby vascular tone.


1982 ◽  
Vol 60 (4) ◽  
pp. 659-669 ◽  
Author(s):  
Ian Orchard

The biogenic amine octopamine is widely distributed within the nervous system of invertebrates. This review examines the role of octopamine in insects and shows that octopamine can act as a neurotransmitter, a neurohormone, and a neuromodulator. Examples of its neurotransmitter role are found in the firefly lantern and also possibly in the glandular lobe of the corpora cardiaca of locusts. Octopamine is also present in the haemolymph of cockroaches and locusts where it functions as a neurohormone, controlling the release of trehalose and lipid from fat body. In locusts, an identified octopaminergic neuron innervates the extensor-tibiae muscle of the hind legs. This neuron inhibits a myogenic rhythm of contraction and relaxation found in a proximal bundle of muscle fibers, and modulates the activity expressed by motoneurons which innervate the extensor-tibiae muscle. Octopamine is, therefore, a neuromodulator in this system. The functional significance of octopamine in insects is discussed with special reference to its association with general arousal phenomena.


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