The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy.

As exceptionally calcium selective store-operated channels, Orai channels play a prominent role in cellular calcium signaling. While most studied in the immune system, we are beginning to recognize that Orai1 provides unique calcium signaling pathways in numerous tissue contexts. To assess the involvement of Orai1 in cardiac hypertrophy we used transverse aortic constriction to model pressure overload cardiac hypertrophy and heart failure in Orai1 deficient mice. We demonstrate that Orai1 deficient mice have significantly decreased survival in this pressure overload model. Transthoracic echocardiography reveals that Orai1 deficient mice develop rapid dilated cardiomyopathy, with greater loss of function, and histological and molecular data indicate that this pathology is associated with significant apoptosis, but not major differences in cellular hypertrophy, fibrosis, and some major hypertrophic makers. Orai1 represents a crucial calcium entry mechanism in the compensation of the heart to pressure overload over-load, and the development of dilated cardiomyopathy.

Cardioprotective signaling by endothelin.

The endothelin axis promotes vasoconstriction, suggesting that antagonists of endothelin signaling might be useful in treatment of heart failure. However, promising results from animal trials have not been recapitulated in heart failure patients. Here we review the role of major signaling pathways in the heart that are involved in cell survival initiated by ET-1. These pathways include mitogen-activated protein kinase, phosphatidyl inositol-1,4,5-triphosphate kinase (PI3K-AKT), nuclear factor-kappaB (NF-kappaB), and calcineurin signaling. A better understanding of endothelin-mediated signaling in cardiac cell survival may allow a reevaluation of endothelin receptor antagonists (ETRAs) in the treatment of heart failure.

Carbon mass balance methodology to characterize the growth of pigmented marine bacteria under conditions of light cycling.

A carbon mass balance methodology employing minimal measurements was applied to heterotrophic and photoheterotrophic marine bacteria grown under constant dilution and exposed to 12-h intervals of light or darkness. Carbon mass balance calculations using measurements taken every 3 h closed to within 93-103% using dissolved organic carbon, biomass carbon and CO2 production data only, indicating that background interference from dissolved inorganic carbon variations in the amended seawater medium was not significant. Neither strain was observed to sustain a net CO2 fixation using paramagnetic measurement of oxygen uptake rates (OUR), indicating a need for more sensitive on-line measurement techniques for OUR. Photoheterotrophic growth demonstrated lower carbon-mole biomass yields (0.41+/-0.026 vs. 0.64+/-0.013 mol mol(-1)) despite higher specific glucose uptake rates (0.025 vs. 0.02 mol mol(-1) h(-1)), suggesting that bioreactor-based study of marine bacteria can present growth modes that are different from those encountered in the marine environment.