Abstract
our studies, septic shock was induced in adult rats by the injection of lipopolysaccharide (LPS). In this model, ventricular action potential is shorter, the calcium signal and the associated twitch contraction are smaller. The sarcoplasmic reticulum (SR) is the major regulator of intracellular calcium, and impairment of its ability to handle calcium could play an important role in our heart failure model. Therefore, experiments investigating the SR calcium content were conducted using freshly isolated ventricular myocytes by measuring the contractures induced by caffeine. In the LPS group, the rate and amount of refilling of SR calcium content was reduced. This observation suggested a reduced uptake of calcium, perhaps due to a decreased phosphorylation of phospholaman (PLB). Western immunoblotting analysis of isolated SR vesicles showed no significant difference in amount of total PLB, but the proportion of phosphorylated PLB was significantly smaller in the LPS group. This implies that the pumping activity of sarcoplasmic reticulum ATPases is reduced in our LPS model, and this contributes to the calcium mishandling of the SR and ultimately to the impaired twitch contraction.
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