Phospholamban and cardiac function: a comparative perspective in vertebrates.

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).

Phospholamban (PLN) is a small phosphoprotein closely associated withthe cardiac sarcoplasmic reticulum (SR). Dephosphorylated PLN tonicallyinhibits the SR Ca-ATPase (SERCA2a), while phosphorylation at Ser16 byPKA and Thr17 by Ca2+/calmodulin-dependent protein kinase (CaMKII)relieves the inhibition, and this increases SR Ca2+ 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 significanceof PLN in vertebrate cardiac physiology. We will refer to the huge literatureon mammals in order to describe the molecular characteristics of thisprotein, its interaction with SERCA2a and its role in the regulation of themechanic and the electric performance of the heart under basal conditions,in the presence of chemical and physical stresses, such as b-adrenergicstimulation, response to stretch, force–frequency relationship and intracellularacidosis. Our aim is to provide the basis to discuss the role of PLNalso on the cardiac function of nonmammalian vertebrates, because so farthis aspect has been almost neglected. Accordingly, when possible, the literatureon PLN will be analysed taking into account the nonuniform cardiacstructural and functional characteristics encountered in ectothermicvertebrates, such as the peculiar and variable organization of the SR, thelarge spectrum of response to stresses and the disaptive absence of crucialproteins (i.e. haemoglobinless and myoglobinless species).