Altered Na/Ca exchange distribution and activity in ventricular myocytes from failing hearts

In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (I(NCX)) and l-type Ca current (I(Ca)) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca](i)) was monitored simultaneously using fluo-4. I(NCX) was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell I(NCX) was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of I(NCX) and I(Ca) away from the T tubules to the cell surface and an increase in t-tubular I(NCX)/I(Ca) density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular I(NCX) in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between I(NCX) and [Ca](i), which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes

Tess data for asteroseismology: Timing verification

The Transiting Exoplanet Survey Satellite (TESS) is NASA´s latest space telescope dedicated to the discovery of transiting exoplanets around nearby stars. Besides the main goal of the mission, asteroseismology is an important secondary goal and very relevant for the high-quality time series that TESS will make during its two-year all-sky survey. Using TESS for asteroseismology introduces strong timing requirements, especially for coherent oscillators. Although the internal clock on board TESS is precise in its own time, it might have a constant drift. Thus, it will need calibration, or else offsets might inadvertently be introduced. Here, we present simultaneous ground- and space-based observations of primary eclipses of several binary systems in the Southern ecliptic hemisphere, used to verify the reliability of the TESS timestamps. From 12 contemporaneous TESS/ground observations, we determined a time offset equal to 5.8 ± 2.5 s, in the sense that the barycentric time measured by TESS is ahead of real time. The offset is consistent with zero at the 2.3σ level. In addition, we used 405 individually measured mid-eclipse times of 26 eclipsing binary stars observed solely by TESS in order to test the existence of a potential drift with a monotonic growth (or decay) affecting the observations of all stars. We find a drift corresponding to σ drift = 0.009 ± 0.015 s day-1. We find that the measured offset is of a size that will not become an issue for comparing ground-based and space data for coherent oscillations for most of the targets observed with TESS.Fil: Essen, Carolina von. University Aarhus; DinamarcaFil: Lund, Mikkel N.. University Aarhus; DinamarcaFil: Handberg, Rasmus. University Aarhus; DinamarcaFil: Sosa, Marina Soledad. University Aarhus; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Gadeberg, Julie Thiim. University Aarhus; DinamarcaFil: Kjeldsen, Hans. University Aarhus; DinamarcaFil: Vanderspek, Roland K.. Massachusetts Institute of Technology; Estados UnidosFil: Mortensen, Dina S.. University Aarhus; DinamarcaFil: Mallonn, M.. Leibniz Institute for Astrophysics Potsdam; AlemaniaFil: Mammana, Luis Antonio. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Morgan, Edward H.. Massachusetts Institute of Technology; Estados UnidosFil: Villaseñor, Jesus Noel S.. Massachusetts Institute of Technology; Estados UnidosFil: Fausnaugh, Michael M.. Massachusetts Institute of Technology; Estados UnidosFil: Ricker, George R.. Massachusetts Institute of Technology; Estados Unido

The Effects of Aging on the Regulation of T-Tubular i Ca by Caveolin in Mouse Ventricular Myocytes

Aging is associated with diminished cardiac function in males. Cardiac excitation-contraction coupling in ventricular myocytes involves Ca influx via the Ca current (ICa) and Ca release from the sarcoplasmic reticulum, which occur predominantly at t-tubules. Caveolin-3 regulates t-tubular ICa, partly through protein kinase A (PKA), and both ICa and caveolin-3 decrease with age. We therefore investigated ICa and t-tubule structure and function in cardiomyocytes from male wild-type (WT) and caveolin-3-overexpressing (Cav-3OE) mice at 3 and 24 months of age. In WT cardiomyocytes, t-tubular ICa-density was reduced by ~50% with age while surface ICa density was unchanged. Although regulation by PKA was unaffected by age, inhibition of caveolin-3-binding reduced t-tubular ICa at 3 months, but not at 24 months. While Cav-3OE increased cardiac caveolin-3 protein expression ~2.5-fold at both ages, the age-dependent reduction in caveolin-3 (WT ~35%) was preserved in transgenic mice. Overexpression of caveolin-3 reduced t-tubular ICa density at 3 months but prevented further ICa loss with age. Measurement of Ca release at the t-tubules revealed that the triggering of local Ca release by t-tubular ICa was unaffected by age. In conclusion, the data suggest that the reduction in ICa density with age is associated with the loss of a caveolin-3-dependent mechanism that augments t-tubular ICa density