Biomedical subjects

R Napolitano

Publications and source records attributed to R Napolitano.

3 recordsLinked to original sources

PubMed1992

Phosphorylation of phospholamban in the intact heart. A study on the physiological role of the Ca(2+)-calmodulin-dependent protein kinase system.

The aim of the present study was to further elucidate the physiological role of the calcium-calmodulin (Ca(2+)-Cm)-dependent protein kinase system on phospholamban phosphorylation in the intact functioning heart. The effect of increasing extracellular calcium concentration [Ca]o on phospholamban phosphorylation (PHPL) was studied under different experimental conditions: (a) regular twitches and ryanodine induced-tetani both in the presence and in the absence of 3 x 10(-8) M isoproterenol and (b) Post-stimulation potentiation (PSP), i.e. the potentiation of contractility that follows a period of rapid repetitive stimulation. In the regular twitch, the increase in [Ca]o enhanced contractility both, in the absence and in the presence of beta-stimulation without changing basal or isoproterenol stimulated cAMP levels respectively. This increase in contractility was accompanied by a significant enhancement of PHPL-from 90.6 +/- 16.4 to 216 +/- 35.2 pmols 32Pi/mg protein at 0.25 and 3.85 mM [Ca]o respectively-only when isoproterenol was present. The calmodulin antagonist W-7 significantly decreased the isoproterenol-induced phosphorylation of phospholamban at [Ca]o 1.35 mM. Similar results were obtained under tetanic conditions. When myocardial contractility was enhanced by PSP up to ten-times with respect to the regular twitch, no detectable effect in PHPL was observed. Indirect evidence obtained from skinned rat cardiac trabeculae suggested that the failure of the cAMP-independent mechanisms to phosphorylate phospholamban is not related to a deficient increase in intracellular calcium. The results support the notion that the increase in intracellular calcium induces an increase in PHPL only at high intracellular cAMP levels.

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PubMed1991

Decrease in tetanic tension elicited by beta-adrenergic stimulation.

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.

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PubMedDate not supplied

Characteristics of ryanodine-induced tetani in the perfused rat heart. Tetanic tension is not the highest force that cardiac muscle can generate.

The aim of the present study was to elucidate the conditions required to obtain tetanic contractions in rat intact heart and to investigate whether tetanic tension was actually the maximal tension that isolated rat heart is able to generate. Experiments were performed on isolated rat hearts (Langendorff technique) perfused at constant coronary flow (8-9 ml/min). Rapid repetitive stimulation (400 to 3000 pulses/min) failed to elicit a fused tetanus. The first twitch that occurred at the end of the rapid stimulation period was a potentiated beat (PSP) of significantly greater magnitude than that of the regular twitch. This potentiation declined in successive beats. When rapid electrical stimulation (600 to 3000 pulses/min) was applied to hearts treated with 5 x 10(-6) M ryanodine, the result was a fused and steady tetanic tension. Ryanodine suppressed PSP. Tetanic tension could be graded by stepwise increase of [Ca2+]o from 0.25 to 5 mM. Maximal tetanic tension occurred at a [Ca2+]o between 3.85 and 5 mM. At any of the [Ca2+]o, tetanic tension was significantly greater than the tension of the twitch obtained at approximately the natural frequency of rat heart in the intact animal (250 beats/min) but it did not differ significantly from the twitch obtained at 100 beats/min. Moreover, the tension of PSP at 0.25 and 1.35 mM [Ca2+]o was significantly greater than the maximal tetanic tension that could be obtained. Similar results to that obtained with ryanodine, were obtained in additional experiments in which caffeine was used to evoke tetanic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

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