Emerging views of how changes in T3 influence prenatal metabolic maturation.
Published in The Journal of physiology
Tissue-specific deletion of mouse basolateral uniporter LAT4 (Slc43a2) reveals its crucial role in small intestine and k...
Published in The Journal of physiology
LAT4 is a broadly expressed uniporter selective for essential branched chain amino acids, methionine and phenylalanine that is involved in epithelial transport. Its global deletion leads to an early malnutrition-like phenotype and death within 10 days after birth. Here we tested the impact of deleting LAT4 selectively in mouse intestine. This affec...
Cardiomyopathy in obesity, insulin resistance and diabetes.
Published in The Journal of physiology
The prevalence of obesity, insulin resistance and diabetes is increasing rapidly. Most patients with these disorders have hypertriglyceridaemia and increased plasma levels of fatty acids, which are taken up and stored in lipid droplets in the heart. Intramyocardial lipids that exceed the capacity for storage and oxidation can be lipotoxic and induc...
Drugging transcription in heart failure.
Published in The Journal of physiology
Advances in our understanding of the basic biology and biochemistry of chromatin structure and function at genome scales has led to tremendous growth in the fields of epigenomics and transcriptional biology. While it has long been appreciated that transcriptional pathways are dysregulated in failing hearts, only recently has the idea of disrupting ...
Endothelial cell-cardiomyocyte crosstalk in heart development and disease.
Published in The Journal of physiology
The crosstalk between endothelial cells and cardiomyocytes has emerged as a requisite for normal cardiac development, but also a key pathogenic player during the onset and progression of cardiac disease. Endothelial cells and cardiomyocytes are in close proximity and communicate through the secretion of paracrine signals, as well as through direct ...
PKA phosphorylation underlies functional recruitment of sarcolemmal SK2 channels in ventricular myocytes from hypertroph...
...Published in The Journal of physiology
Small-conductance Ca2+ -activated K+ (SK) channels expressed in ventricular myocytes are dormant in health, yet become functional in cardiac disease. SK channels are voltage independent and their gating is controlled by intracellular [Ca2+ ] in a biphasic manner. Submicromolar [Ca2+ ] activates the channel via constitutively-bound calmodulin, where...
Neurocardiac regulation: from cardiac mechanisms to novel therapeutic approaches.
Published in The Journal of physiology
Cardiac sympathetic overactivity is a well-established contributor to the progression of neurogenic hypertension and heart failure, yet the underlying pathophysiology remains unclear. Recent studies have highlighted the importance of acutely regulated cyclic nucleotides and their effectors in the control of intracellular calcium and exocytosis. Eme...
Calcium modulation of cardiac sodium channels.
Published in The Journal of physiology
Modification of voltage-gated Na+ channel (NaV ) function by intracellular Ca2+ has been a topic of much controversy. Early studies relied on measuring NaV function in the absence or presence of intracellular Ca2+ , and generated seemingly disparate results. Subsequent investigations revealed the mechanism(s) of Ca2+ -driven NaV modulation are comp...
Regulation of cardiomyocyte maturation during critical perinatal window.
Published in The Journal of physiology
A primary limitation in the use of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) for both patient health and scientific investigation is the failure of these cells to achieve full functional maturity. In vivo, cardiomyocytes undergo numerous adaptive structural, functional and metabolic changes during maturation. By contrast, PSC-CMs fail ...
Calcineurin-AKAP interactions: therapeutic targeting of a pleiotropic enzyme with a little help from its friends.
Published in The Journal of physiology
The ubiquitous Ca2+ /calmodulin-dependent phosphatase calcineurin is a key regulator of pathological cardiac hypertrophy whose therapeutic targeting in heart disease has been elusive due to its role in other essential biological processes. Calcineurin is targeted to diverse intracellular compartments by association with scaffold proteins, including...
