Decrease in tetanic tension elicited by beta-adrenergic stimulation

Abstract

The effect of beta-adrenergic stimulation on tetanic tension (TT), maximal rate of rise of tension (+TT) and phospholamban (PHL) phosphorylation were studied in the perfused rat heart. 3 x 10(-8) M isoproterenol perfused at different [Ca2+]o 0.25, 1.35 and 3.85 mM, significantly decreased TT while increased +TT and PHL phosphorylation at the three [Ca2+]o studied. Regression lines of the relationship between +TT and TT from individual data obtained at each [Ca2+]o in the presence and in the absence of isoproterenol, show that for the same level of +TT, TT is lower in the presence of isoproterenol, i.e. at high levels of PHL phosphorylation. The slopes of the lines were 0.137 s and 0.427 s (P less than 0.05) in the presence and absence of isoproterenol respectively. The decrease in TT produced by the beta-agonist can be attributed to its relaxant action prevailing over its inotropic effect and may represent the mechanical expression of the enhanced phosphorylation of phospholamban.

Role of Ca2+-calmodulin dependent phospholamban phosphorylation on the relaxant effect of ?-adrenergic agonists

“…In the intact heart evidence has been obtained about the lack of Ca2+-calmodulin dependent phospholamban phosphorylation in response to increases in [Ca2+]i produced by cAMP independent mechanisms [11,14,15,17,18]. Other experiments seem to indicate however that the Ca2+-calmodulin system does phosphorylate phospholamban when the heart is stimulated by agents that increase cAMR Experiments from our own and other laboratories have reported a [Ca]o dependence of isoproterenol induced phospholamban phosphorylation in the intact heart [11,15,17,18]. Whether this calcium dependence reflects the activity of the Ca2+-calmodulin dependent protein kinase cannot be unequivocally ascertained from those experiments.…”

“…Phosphorylation of phospholamban has been shown not to occur after maneuvers which raise intracellular Ca 2+ by cAMP independent mechanisms. These interventions failed also to affect myocardial relaxation [11,14,15,17,18]. Wegener et al [19] have identified not only serine 16 but threonine 17 as the amino acids of phospholamban phosphorylated in response to 13-adrenergic stimulation in intact ventricles.…”