Protein kinase A-dependent modulation of Ca<sup>2+</sup>sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin

Matsuba, Douchi; Terui, Takako; Tanaka, Hiroyuki; Ojima, Takao; Ohtsuki, Iwao; Ishiwata, Shin’ichi; Kurihara, Satoshi; Fukuda, Norio

doi:10.1083/jcb1855oia12

Cited by 4 publications

(9 citation statements)

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“…In the current study, IAANS was attached to residue 53, which, because of its location within the molecule, does not interact with other regions of cTnC or with cTnI/cTnT during Ca 2+ activation (Davis et al, 2007). The decrease in the Ca 2+ affinity of the mammalian cTn complex with PKA treatment is consistent with the decrease in Ca 2+ sensitivity of force generation that occurs when mammalian cardiac tissue is treated with PKA (Fentzke et al, 1999;Matsuba et al, 2009). This change in cTn function is thought to be responsible for the increased rate of muscle relaxation that occurs following b-adrenergic stimulation in the heart (Kentish et al, 2001;Li et al, 2004;Rarick et al, 1999;Solaro and Rarick, 1998).…”

Section: Discussionsupporting

confidence: 55%

“…When Ser23 and Ser24 are phosphorylated, this interaction between cTnI and cTnC is thought to weaken, leading to a reduction in the Ca 2+ affinity of the regulatory domain of cTnC (Chandra et al, 1997;Robertson et al, 1982;Solaro et al, 2008). This translates into a decrease in the Ca 2+ sensitivity of force generation and increased rates of muscle relaxation (Kentish et al, 2001;Li et al, 2004;Matsuba et al, 2009;Rarick et al, 1999;Solaro and Rarick, 1998). The change in cTnC Ca 2+ affinity upon cTnI phosphorylation illustrates the fact that changes in the structural properties of cTnI can alter the ability of the cTn complex to be activated by Ca…”

Section: Introductionmentioning

confidence: 99%

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The influence of trout cardiac troponin I and PKA phosphorylation on the Ca2+ affinity of the cardiac troponin complex

Kirkpatrick

Robertson

Klaiman

et al. 2011

Journal of Experimental Biology

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SUMMARYThe trout heart is 10-fold more sensitive to Ca 2+ than the mammalian heart. This difference is due, in part, to cardiac troponin C (cTnC) from trout having a greater Ca 2+ affinity than human cTnC. To determine what other proteins are involved, we cloned cardiac troponin I (cTnI) from the trout heart and determined how it alters the Ca 2+ affinity of a cTn complex containing all mammalian components (mammalian cTn). Ca 2+ activation of the complex was characterized using a human cTnC mutant that contains anilinonapthalenesulfote iodoacetamide attached to Cys53. When the cTn complex containing labeled human cTnC was titrated with Ca 2+, its fluorescence changed, reaching an asymptote upon saturation. Our results reveal that trout cTnI lacks the N-terminal extension found in cTnI from all other vertebrate groups. This protein domain contains two targets (Ser23 and Ser24) for protein kinase A (PKA) and protein kinase C. When these are phosphorylated, the rate of cardiomyocyte relaxation increases. When rat cTnI in the mammalian cTn complex was replaced with trout cTnI, the Ca 2+ affinity was increased ~1.8-fold. This suggests that trout cTnI contributes to the high Ca 2+ sensitivity of the trout heart. Treatment of the two cTn complexes with PKA decreased the Ca 2+ affinity of both complexes. However, the change for the complex containing rat cTnI was 2.2-fold that of the complex containing trout cTnI. This suggests that the phosphorylation of trout cTnI does not play as significant a role in regulating cTn function in trout.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

The influence of trout cardiac troponin I and PKA phosphorylation on the Ca2+ affinity of the cardiac troponin complex

Kirkpatrick

Robertson

Klaiman

et al. 2011

Journal of Experimental Biology

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“…; Matsuba et al . ), but neither protein is phosphorylated in skeletal muscle (Stull & High, ; Gruen et al . ; Matsuba et al .…”

Section: Introductionmentioning

confidence: 99%

β‐Adrenergic modulation of skeletal muscle contraction: key role of excitation–contraction coupling

Cairns

Borrani

2015

The Journal of Physiology

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channels contributes to force potentiation in diaphragm and amphibian muscle, but not mammalian limb muscle. Phosphorylation of phospholamban increases SR Ca 2+ pump activity in slow-twitch fibres but does not augment force; this process accelerates relaxation and may depress force. Greater Ca 2+ loading of SR may assist force potentiation in fast-twitch muscle. Some human studies show no significant force potentiation which appears to be related to the β-agonist concentration used. Indeed high-dose β-agonists (ß0.1 μM) enhance SR Ca 2+ -release rates, maximum voluntary contraction strength and peak Wingate power in trained humans. The combined findings can explain how adrenaline/β-agonists influence muscle performance during exercise/stress in humans. PKA, cAMP-dependent protein kinase; PLB, phospholamban; RyR1, skeletal muscle ryanodine receptor; SERCA, Ca 2+ pump; t-tubule, transverse tubule. P indicates phosphorylation site.

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“…The suggested mechanism is a cGMP/PKG-mediated phosphorylation of phospholamban and troponin I. Indeed, PLB on Ser 16 and troponin I on Ser 23/24 are phosphorylated by PKG with rates similar to that of PKA and about 100-fold slower than that of PKA, respectively (Raeymaekers et al 1988;Matsuba et al 2009). In accordance to that, in our study, CNP tended to increase phosphorylation of PLB and TnI, reaching significance in the concomitant presence of the PDE4 inhibitor rolipram (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Both proteins have a direct role in the establishment of the functional response, and activation of human cardiac 5-HT 4 receptors has been correlated with their phosphorylation (Gergs et al 2009). TnI is a member of the troponin protein complex of the contractile machinery in the cell, which upon phosphorylation decreases myofibrillar Ca 2+ sensitivity, resulting in a faster relaxation, thus a lusitropic response (Matsuba et al 2009). PKA phosphorylation of PLB Ser 16 causes the protein to release its inhibition on SERCA, the sarcoplasmic reticulum (SR) Ca 2+ pump, thereby allowing a faster reuptake of Ca 2+ into the SR.…”

Section: Discussionmentioning

confidence: 99%

Influence of phosphodiesterases and cGMP on cAMP generation and on phosphorylation of phospholamban and troponin I by 5-HT4 receptor activation in porcine left atrium

Weninger

Maeyer

Lefebvre

2013

Naunyn-Schmiedeberg's Arch Pharmacol

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Our objective was to investigate the role of phosphodiesterase (PDE)3 and PDE4 and cGMP in the control of cAMP metabolism and of phosphorylation of troponin I (TnI) and phospholamban (PLB) when 5-HT 4 receptors are activated in pig left atrium. Electrically paced porcine left atrial muscles, mounted in organ baths, received stimulators of particulate guanylyl cyclase (pGC) or soluble guanylyl cyclase (sGC) and/or specific PDE inhibitors followed by 5-HT or the 5-HT 4 receptor agonist prucalopride. Muscles were freezeclamped at different moments of exposure to measure phosphorylation of the cAMP/protein kinase A targets TnI and PLB by immunoblotting and cAMP levels by enzyme immunoassay. Corresponding with the functional results, 5-HT only transiently increased cAMP content, but caused a less quickly declining phosphorylation of PLB and did not significantly change TnI phosphorylation. Under combined PDE3 and PDE4 inhibition, the 5-HT-induced increase in cAMP levels and PLB phosphorylation was enhanced and sustained, and TnI phosphorylation was now also increased. Responses to prucalopride per se and the influence thereupon of PDE3 and PDE4 inhibition were similar except that responses were generally smaller. Stimulation of pGC together with PDE4 inhibition increased 5-HT-induced PLB phosphorylation compared to 5-HT alone, consistent with functional responses. sGC stimulation hastened the fade of inotropic responses to 5-HT, while cAMP levels were not altered. PDE3 and PDE4 control the cAMP response to 5-HT 4 receptor activation, causing a dampening of downstream signalling. Stimulation of pGC is able to enhance inotropic responses to 5-HT by increasing cAMP levels, while sGC stimulation decreases contraction to 5-HT cAMP independently.

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Protein kinase A-dependent modulation of Ca²⁺sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin

Cited by 4 publications

References 1 publication

The influence of trout cardiac troponin I and PKA phosphorylation on the Ca2+ affinity of the cardiac troponin complex

The influence of trout cardiac troponin I and PKA phosphorylation on the Ca2+ affinity of the cardiac troponin complex

β‐Adrenergic modulation of skeletal muscle contraction: key role of excitation–contraction coupling

Influence of phosphodiesterases and cGMP on cAMP generation and on phosphorylation of phospholamban and troponin I by 5-HT4 receptor activation in porcine left atrium

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Protein kinase A-dependent modulation of Ca2+sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin

Cited by 4 publications

References 1 publication

The influence of trout cardiac troponin I and PKA phosphorylation on the Ca2+ affinity of the cardiac troponin complex

The influence of trout cardiac troponin I and PKA phosphorylation on the Ca2+ affinity of the cardiac troponin complex

β‐Adrenergic modulation of skeletal muscle contraction: key role of excitation–contraction coupling

Influence of phosphodiesterases and cGMP on cAMP generation and on phosphorylation of phospholamban and troponin I by 5-HT4 receptor activation in porcine left atrium

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Protein kinase A-dependent modulation of Ca²⁺sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin