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).