Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia.

Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca(2+)]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca(2+)]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca(2+). Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca(2+)]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na(+)-Ca(2+) exchange. These results suggest that LQTS mutations act partly on cytosolic Ca(2+) cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.

Photosynthetic responses of two eucalypts to industrial-age changes in atmospheric [CO2] and temperature.

The unabated rise in atmospheric [CO(2)] is associated with increased air temperature. Yet, few CO(2)-enrichment studies have considered pre-industrial [CO(2)] or warming. Consequently, we quantified the interactive effects of growth [CO(2)] and temperature on photosynthesis of faster-growing Eucalyptus saligna and slower-growing E. sideroxylon. Well-watered and -fertilized tree seedlings were grown in a glasshouse at three atmospheric [CO(2)] (290, 400, and 650 µL L(-1)), and ambient (26/18 °C, day/night) and high (ambient + 4 °C) air temperature. Despite differences in growth rate, both eucalypts responded similarly to [CO(2)] and temperature treatments with few interactive effects. Light-saturated photosynthesis (A(sat)) and light- and [CO(2)]-saturated photosynthesis (A(max) ) increased by ∼ 50% and ∼ 10%, respectively, with each step-increase in growth [CO(2)], underpinned by a corresponding 6-11% up-regulation of maximal electron transport rate (J(max)). Maximal carboxylation rate (V(cmax)) was not affected by growth [CO(2)]. Thermal photosynthetic acclimation occurred such that A(sat) and A(max) were similar in ambient- and high-temperature-grown plants. At high temperature, the thermal optimum of A(sat) increased by 2-7 °C across [CO(2)] treatments. These results are the first to suggest that photosynthesis of well-watered and -fertilized eucalypt seedlings will remain strongly responsive to increasing atmospheric [CO(2)] in a future, warmer climate.