Adrenergic effects on force-frequency relationship: a pivotal role for the cardiac intrinsic systems

Mattera, Giovan Giuseppe; Vanoli, Emilio; Martinez, V.; Luciani, Michelangelo; Falco, Teresa; Borsini, Franco

doi:10.1111/j.1748-1716.2011.02266.x

“…The change in force production and contractility with increasing heart rate, or contraction frequency, is termed force-frequency relationship (FFR) and is classified as positive, primary-phase negative, secondary-phase negative or overall negative (Endoh 2004). Changes in force development depend on an intact adrenergic system (Mattera et al 2011), and are directly related to changes in intracellular Ca 2+ transients (Yue 1992). mammalian vs. nonmammalian and small rodents vs. large rodents) and on the cardiac tissue (atria vs. ventricle).…”

Section: Force-frequency Relationshipmentioning

confidence: 99%

“…In rodents, this relationship tends to be more variable, while larger mammals generally show a positive FFR. Changes in force development depend on an intact adrenergic system (Mattera et al 2011), and are directly related to changes in intracellular Ca 2+ transients (Yue 1992). In this context, the species-specific functional arrangement of the SR, together with SER-CA2a-PLN association, is required to play a crucial role.…”

Section: Force-frequency Relationshipmentioning

confidence: 99%

Phospholamban and cardiac function: a comparative perspective in vertebrates

Cerra¹,

Imbrogno

²

2012

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Phospholamban (PLN) is a small phosphoprotein closely associated with the cardiac sarcoplasmic reticulum (SR). Dephosphorylated PLN tonically inhibits the SR Ca-ATPase (SERCA2a), while phosphorylation at Ser16 by PKA and Thr17 by Ca 2+ /calmodulin-dependent protein kinase (CaMKII) relieves the inhibition, and this increases SR Ca 2+ uptake. For this reason, PLN is one of the major determinants of cardiac contractility and relaxation. In this review, we attempted to highlight the functional significance of PLN in vertebrate cardiac physiology. We will refer to the huge literature on mammals in order to describe the molecular characteristics of this protein, its interaction with SERCA2a and its role in the regulation of the mechanic and the electric performance of the heart under basal conditions, in the presence of chemical and physical stresses, such as b-adrenergic stimulation, response to stretch, force-frequency relationship and intracellular acidosis. Our aim is to provide the basis to discuss the role of PLN also on the cardiac function of nonmammalian vertebrates, because so far this aspect has been almost neglected. Accordingly, when possible, the literature on PLN will be analysed taking into account the nonuniform cardiac structural and functional characteristics encountered in ectothermic vertebrates, such as the peculiar and variable organization of the SR, the large spectrum of response to stresses and the disaptive absence of crucial proteins (i.e. haemoglobinless and myoglobinless species). Intracellular [Ca 2+ ] oscillation, a major determinant of the myocardial contraction/relaxation cycle, is governed by a number of transporters. They include sarcolemmal L-type Ca 2+ channels, Na + /Ca 2+ exchanger, the plasma membrane Ca 2+ pump, several sarcoplasmic reticulum (SR) membrane proteins such as the ryanodine receptors, as well as the complex formed by the sarcoplasmic membrane Ca 2+ pump (SERCA2a) and its associated regulatory protein phospholamban (PLN). The name of this protein, which means 'phosphate receptor' (from phosphate and the Greek word kalbamx = I receive), very appropriately reflects its function. After its discovery by Katz and co-workers in cardiac mammalian microsomes [for complete references, see Katz (2006)], many works have largely demonstrated that, during a normal cardiac cycle, alternate PLN phosphorylation/dephosphorylation determines SERCA2a on/off state, and thus the rate of SR refilling with Ca 2+ , with a consequent strong impact on myocardial relaxation and contraction. At the level of sinoatrial node cells, the SERCA2a-PLN system functions as an intracellular 'Ca 2+ ' clock,

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“…ACCEPTED MANUSCRIPT 13 with a positive correlation between contraction frequency, force development and the magnitude of the intracellular Ca + transient (22,(32)(33). Although Ca + load plays a central role in the force-frequency relationship, Calmodulin has been described to contribute to the frequency-dependent regulation of contraction and relaxation (32).…”

Section: Accepted Manuscriptmentioning

confidence: 97%

Translational assessment of cardiac contractility by echocardiography in the telemetered rat

Tang¹,

Ju²,

Zhao³

et al. 2016

Journal of Pharmacological and Toxicological Methods

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“…Changes in force development depend on an intact adrenergic system (Mattera et al . ), and are directly related to changes in intracellular Ca 2+ transients (Yue ). In this context, the species‐specific functional arrangement of the SR, together with SERCA2a–PLN association, is required to play a crucial role.…”

Section: Contractility and Relaxationmentioning

confidence: 99%

Phospholamban and cardiac function: a comparative perspective in vertebrates

Cerra¹,

Imbrogno

²

2012

View full text Add to dashboard Cite

Phospholamban (PLN) is a small phosphoprotein closely associated with the cardiac sarcoplasmic reticulum (SR). Dephosphorylated PLN tonically inhibits the SR Ca-ATPase (SERCA2a), while phosphorylation at Ser16 by PKA and Thr17 by Ca(2+) /calmodulin-dependent protein kinase (CaMKII) relieves the inhibition, and this increases SR Ca(2+) uptake. For this reason, PLN is one of the major determinants of cardiac contractility and relaxation. In this review, we attempted to highlight the functional significance of PLN in vertebrate cardiac physiology. We will refer to the huge literature on mammals in order to describe the molecular characteristics of this protein, its interaction with SERCA2a and its role in the regulation of the mechanic and the electric performance of the heart under basal conditions, in the presence of chemical and physical stresses, such as β-adrenergic stimulation, response to stretch, force-frequency relationship and intracellular acidosis. Our aim is to provide the basis to discuss the role of PLN also on the cardiac function of nonmammalian vertebrates, because so far this aspect has been almost neglected. Accordingly, when possible, the literature on PLN will be analysed taking into account the nonuniform cardiac structural and functional characteristics encountered in ectothermic vertebrates, such as the peculiar and variable organization of the SR, the large spectrum of response to stresses and the disaptive absence of crucial proteins (i.e. haemoglobinless and myoglobinless species).

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Adrenergic effects on force-frequency relationship: a pivotal role for the cardiac intrinsic systems

Abstract: The F-FR appeared to be constituted by two consecutive mechanisms: first depolarization-rate dependent, and a second catecholamine-dependent. The natural consequence of these observations is that the full expression of F-FR needs an intact adrenergic system.

Cited by 7 publications

References 39 publications

Phospholamban and cardiac function: a comparative perspective in vertebrates

Phospholamban and cardiac function: a comparative perspective in vertebrates

Translational assessment of cardiac contractility by echocardiography in the telemetered rat

Phospholamban and cardiac function: a comparative perspective in vertebrates

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