scholarly journals Ryanodine receptors, voltage-gated calcium channels and their relationship with protein kinase A in the myocardium

2008 ◽  
pp. 141-149
Author(s):  
MM Petrovic ◽  
K Vales ◽  
B Putnikovic ◽  
V Djulejic ◽  
DM Mitrovic
Keyword(s):  
Protein Kinase ◽  
Calcium Channels ◽  
Cardiac Muscle ◽  
Protein Kinase A ◽  
Ryanodine Receptor ◽  
Ryanodine Receptors ◽  
Physiological Role ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Kinase A

We present a review about the relationship between ryanodine receptors and voltage-gated calcium channels in myocardium, and also how both of them are related to protein kinase A. Ryanodine receptors, which have three subtypes (RyR1-3), are located on the membrane of sarcoplasmic reticulum. Different subtypes of voltage-gated calcium channels interact with ryanodine receptors in skeletal and cardiac muscle tissue. The mechanism of excitation-contraction coupling is therefore different in the skeletal and cardiac muscle. However, in both tissues ryanodine receptors and voltage-gated calcium channels seem to be physically connected. FK-506 binding proteins (FKBPs) are bound to ryanodine receptors, thus allowing their concerted activity, called coupled gating. The activity of both ryanodine receptors and voltage-gated calcium channels is positively regulated by protein kinase A. These effects are, therefore, components of the mechanism of sympathetic stimulation of myocytes. The specificity of this enzyme’s targeting is achieved by using different A kinase adapting proteins. Different diseases are related to inborn or acquired changes in ryanodine receptor activity in cardiac myocytes. Mutations in the cardiac ryanodine receptor gene can cause catecholamineprovoked ventricular tachycardia. Changes in phosphorylation state of ryanodine receptors can provide a credible explanation for the development of heart failure. The restoration of their normal level of phosphorylation could explain the positive effect of beta-blockers in the treatment of this disease. In conclusion, molecular interactions of ryanodine receptors and voltage-gated calcium channels with PKA have a significant physiological role. However, their defects and alterations can result in serious disturbances.

mAKAP and the ryanodine receptor are part of a multi-component signaling complex on the cardiomyocyte nuclear envelope

2001 ◽  
Vol 114 (17) ◽  
pp. 3167-3176
Author(s):  
Michael S. Kapiloff ◽  
Nicole Jackson ◽  
Nathan Airhart
Keyword(s):  
Protein Kinase ◽  
Nuclear Envelope ◽  
Protein Kinase A ◽  
Ryanodine Receptor ◽  
Calcium Ion ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Scaffolding Protein ◽  
Signaling Complex ◽  
Kinase A

The physical association of regulatory enzymes and ion channels at relevant intracellular sites contributes to the diversity and specificity of second messenger-mediated signal transduction in cells. mAKAP is a scaffolding protein that targets the cAMP-dependent protein kinase A and phosphodiesterase type 4D3 to the nuclear envelope of differentiated cardiac myocytes. Here we present data that the mAKAP signaling complex also includes nuclear envelope-resident ryanodine receptors and protein phosphatase 2A. The ryanodine receptor is the major cardiac ion channel responsible for calcium-induced calcium release from intracellular calcium ion stores. As demonstrated by a combination of immunohistochemistry and tissue fractionation, mAKAP is targeted specifically to the nuclear envelope, whereas the ryanodine receptor is present at both the sarcoplasmic reticulum and nuclear envelope intracellular membrane compartments. At the nuclear envelope, a subset of cardiac ryanodine receptor is bound to mAKAP and via the association with mAKAP may be regulated by protein kinase A-mediated phosphorylation. By binding protein kinase A and ryanodine receptor, mAKAP may serve as the scaffold for a cAMP- and calcium ion-sensitive signaling complex.

scholarly journals Protein Kinase A Phosphorylation of the Cardiac Calcium Release Channel (Ryanodine Receptor) in Normal and Failing Hearts

2002 ◽  
Vol 278 (1) ◽  
pp. 444-453 ◽  
Author(s):  
Steven Reiken ◽  
Marta Gaburjakova ◽  
Silvia Guatimosim ◽  
Ana M. Gomez ◽  
Jeanine D'Armiento ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Ryanodine Receptor ◽  
Calcium Release ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Kinase A

scholarly journals Stress-induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor

2012 ◽  
Vol 590 (24) ◽  
pp. 6381-6387 ◽  
Author(s):  
Daniel C. Andersson ◽  
Matthew J. Betzenhauser ◽  
Steven Reiken ◽  
Alisa Umanskaya ◽  
Takayuki Shiomi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Ryanodine Receptor ◽  
Muscle Force ◽  
Kinase A

scholarly journals Protein kinase A modulation of CaV1.4 calcium channels

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Lingjie Sang ◽  
Ivy E. Dick ◽  
David T. Yue
Keyword(s):  
Protein Kinase ◽  
Calcium Channels ◽  
Protein Kinase A ◽  
Kinase A

scholarly journals A mechanism of ryanodine receptor modulation by FKBP12/12.6, protein kinase A, and K201

2009 ◽  
Vol 85 (1) ◽  
pp. 68-78 ◽  
Author(s):  
L. M. Blayney ◽  
J.-L. Jones ◽  
J. Griffiths ◽  
F. A. Lai
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Ryanodine Receptor ◽  
Receptor Modulation ◽  
Kinase A

Overexpression of Dd PK2 protein kinase causes rapid development and affects the intracellular cAMP pathway of Dictyostelium discoideum

Development ◽  
1992 ◽  
Vol 115 (3) ◽  
pp. 785-790 ◽  
Author(s):  
C. Anjard ◽  
S. Pinaud ◽  
R.R. Kay ◽  
C.D. Reymond
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Rapid Development ◽  
Physiological Role ◽  
Intracellular Camp ◽  
Developmentally Regulated ◽  
K Cells ◽  
Frame Shift ◽  
Camp Levels ◽  
Kinase A

The Dd PK2 gene codes for a putative protein of 648 amino acids with a C-terminal half sharing high homology with protein kinase A catalytic subunits from other organisms. In order to find out more about the physiological role of the Dd PK2 kinase, its gene, and a version having a frame shift mutation in the middle of the catalytic region, were overexpressed in developing Dictyostelium cells. Both the intact gene (K-) and the frame shift mutant (Kdel-) caused rapid development with spores formed in 16–18 hours compared to the 24 hours required by their parent. This result was confirmed by the pattern of expression of some developmentally regulated genes. Other rapid developing strains (rde) are activated in the cAMP second messenger system. Both K- and Kdel-containing strains have lower cAMP levels than the parental strain during late development, thus resembling rdeC mutants. K-cells (but not Kdel-cells) produced bizarre fruiting bodies with many prostrate forms. The parallel with rde mutants was confirmed by demonstrating that K-cells are able to form spores in submerged monolayer culture. Furthermore, K-cells have about four times more protein kinase A (cAPK) activity than wild-type cells. These results indicate that the N-terminal domain of Dd PK2 is sufficient to influence cAMP levels and to provoke rapid development, whereas kinase activity seems to be required for the sporogenous phenotype. The association between elevated cAPK and Dd PK2 overexpression phenotype further indicates a role for cAPK in the formation of spores.

scholarly journals TSH Regulates Pendrin Membrane Abundance and Enhances Iodide Efflux in Thyroid Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 512-521 ◽  
Author(s):  
Liuska Pesce ◽  
Aigerim Bizhanova ◽  
Juan Carlos Caraballo ◽  
Whitney Westphal ◽  
Maria L. Butti ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Phosphorylation Site ◽  
Physiological Role ◽  
Thyroid Cells ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Rat Thyroid ◽  
Kinase A

Thyroid hormones are essential for normal development and metabolism. Their synthesis requires transport of iodide into thyroid follicles. The mechanisms involving the apical efflux of iodide into the follicular lumen are poorly elucidated. The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. We determined whether TSH regulates pendrin abundance at the plasma membrane and whether this influences iodide efflux. Results of immunoblot and immunofluorescence experiments reveal that TSH and forskolin rapidly increase pendrin abundance at the plasma membrane through the protein kinase A pathway in PCCL-3 rat thyroid cells. The increase in pendrin membrane abundance correlates with a decrease in intracellular iodide as determined by measuring intracellular 125iodide and can be inhibited by specific blocking of pendrin. Elimination of the putative protein kinase A phosphorylation site T717A results in a diminished translocation to the membrane in response to forskolin. These results demonstrate that pendrin translocates to the membrane in response to TSH and suggest that it may have a physiological role in apical iodide transport and thyroid hormone synthesis.

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