The U.S. Department of Energy's Office of Scientific and Technical Information

The U.S. Department of Energy's Office of Scientific and Technical Information

A reduction of the Ca(2+)-independent transient outward potassium current (I(to)) in epicardial but not in endocardial myocytes of the left ventricle has been observed in cardiac hypertrophy and is thought to contribute to the electrical vulnerability associated with this pathology. In the present study we investigated the molecular mechanisms underlying regional alterations in I(to) in hypertrophied hearts of spontaneously hypertensive rats (SHR) using the whole-cell patch-clamp technique, quantitative RT-PCR and heterologous expression of underlying ion channel subunits. I(to) was significantly smaller in epicardial myocytes of SHR than in Wistar-Kyoto (WKY) controls (11.1+/-0.9 pA/pF, n=20 vs. 16.8+/-1.7 pA/pF, n=20, p<0.01), but not different in endocardial myocytes from both groups. Quantitative RT-PCR analysis of the genes encoding I(to) revealed significantly lower levels of Kv4.2 and Kv4.3 mRNA in the epicardial region of SHR rats compared to WKY rats. In contrast, mRNA expression levels of all three splice variants of the beta-subunit KChIP2 were significantly higher in both endo- and epicardial myocytes from SHR than from WKY rats. In parallel, inactivation of I(to), which is negatively modulated by KChIP2, was slowed down in SHR while recovery from inactivation remained unchanged. Heterologous co-expression of increasing amounts of KChIP2b together with a fixed amount of Kv4.2 in Xenopus laevis oocytes revealed a hyperbolic relation of recovery from inactivation and inactivation time constant, demonstrating that KChIP2 preferentially affects inactivation, if its expression level is high. These results suggest that downregulation of I(to) in the left ventricle of SHR is mediated by a reduced expression of Kv4.2 and Kv4.3 (but not of KChIP2), whereas the slower inactivation of I(to) can be explained by increased expression levels of KChIP2 in SHR.

Variable renewable energy availability has increased the volatility in energy prices in most markets. Nuclear power plants, with a large ratio of capital to variable costs, have historically operated as base load energy suppliers but the need for more flexible operation is increasing. We simulate the techno-economic performance of a 950 MW${}_t$ nuclear power plant, based on the Westinghouse lead-cooled fast reactor, coupled with molten salt thermal storage as a method for flexible energy dispatch. We use the System Advisor Model to model the nuclear reactor thermal power input and power cycle operating modes. We combine this robust engineering model with a mixed-integer linear program model for optimized dispatch scheduling. We then simulate the coupled nuclear and thermal storage system under different market scenarios with varying price volatility. We find that the coupled plant outperforms the base plant under markets where energy price peaks fluctuate by a factor of two or more about the mean price. We show that a calculated power purchase agreement price for the plant improves by up to 10% when operating under California energy market conditions. Sensitivity analysis on the thermal storage cost shows that the optimal design remains unchanged even when doubling costs.