RATIONALE β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs in patients with heart failure, causes potentially arrhythmogenic reductions in slow delayed-rectifier K(+) current (IKs). OBJECTIVE To assess the molecular mechanisms of IKs downregulation caused by chronic β-adrenergic activation, particularly the role of exchan...

Ca2+ is one of the most important and universal intracellular signalling agents, controlling a multitude of vitally important cellular processes (Petersen & Verkhratsky 2016). The regulating cytosolic Ca2+ signals vary enormously with regard to timing, localization and spatial extent, depending on the specific cell type and the function to be controlled (Petersen & Verkhratsky, 2016). Because o...

Calcineurin is a calcium-dependent serine–threonine protein phosphatase. Calcineurin activates the nuclear factor of activated T-cells cytoplasmic (NFAT)c, a transcription factor, by dephosphorylating the protein. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of T-...

The effects of changes in action potential waveform on excitation–contraction coupling in mammalian ventricle were first identified almost 40 years ago.1 Many important details concerning the relationship between action potential duration and tension development have been elucidated.2 Recent work has demonstrated significant effects on the intracellular Ca transient and excitation–contraction c...

Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a tissue microarr...

Renal disease is a common complication of diabetes. The initiating events in diabetic nephropathy are triggered by hyperglycemia and, possibly, advanced glycation end products. Subsequently, excess levels of vasoactive peptides (especially endothelin-1 (ET-1)) accumulate in the diabetic kidney, and there is evidence that these peptides mediate many of the pathophysiological changes associated w...

Development of the heart is complex and cells with different embryonic origins participate in cardiac organogenesis. The first and second heart fields deliver cells to generate the atrial and ventricular chambers and also participate in venous inflow and arterial outflow tract formation. There are also important cellular contributions from two extra-cardiac cell populations, i.e. cardiac neural...