Andrew W Trafford

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The myocardial extracellular matrix (ECM), which preserves the geometry and integrity of the myocardium, is a dynamic structure whose component proteins are maintained by a finely controlled homeostatic balance between deposition and degradation. One of the key targets in cardiology is the elucidation of the molecular mechanisms which mediate pathological(More)
1. Intracellular calcium concentration ([Ca2+]i) and Na(+)-Ca2+ exchange currents were measured in calcium-overloaded voltage-clamped rat ventricular myocytes loaded with the Ca(2+)-sensitive fluorescent indicator indo-1. Sarcoplasmic reticulum (SR) Ca2+ content was measured from the integral of the caffeine-evoked current. In cells that had spontaneous SR(More)
Division of Experimental Cardiology, Dept of Experimental & Clinical Pharmacology, Medical Faculty Mannheim, University of Heidelberg, Mannheim; Dept of Pharmacology & Toxicology, Dresden University of Technology, Dresden, Germany; Dept of Molecular Physiology & Biophysics, Dept of Medicine, Baylor College of Medicine, Houston, TX; Unit of Cardiac(More)
BACKGROUND Delayed afterdepolarizations (DADs) carried by Na(+)-Ca(2+)-exchange current (I(NCX)) in response to sarcoplasmic reticulum (SR) Ca(2+) leak can promote atrial fibrillation (AF). The mechanisms leading to delayed afterdepolarizations in AF patients have not been defined. METHODS AND RESULTS Protein levels (Western blot), membrane currents and(More)
1. The effects of modulating Ca2+-induced Ca2+ release (CICR) in single cardiac myocytes were investigated using low concentrations of caffeine (< 500 microM) in reduced external Ca2+ (0.5 mM). Caffeine produced a transient potentiation of systolic [Ca2+]i (to 800 % of control) which decayed back to control levels. 2. Caffeine decreased the steady-state(More)
There is much evidence showing that some lethal ventricular arrhythmias arise from waves of Ca(2+) release from the sarcoplasmic reticulum (SR) that propagate along cardiac cells. The purpose of this review is to discuss the mechanism of production of these waves and how they depend on the properties of the SR Ca(2+) release channel or ryanodine receptor(More)
Diastolic waves of Ca(2+) release have been shown to activate delayed afterdepolarizations as well as some cardiac arrhythmias. The aim of this study was to investigate whether increasing ryanodine receptor open probability alone or in the presence of beta-adrenergic stimulation produces diastolic Ca release from the sarcoplasmic reticulum (SR). When(More)
In this article we review the role of the Ryanodine Receptor (RyR) in cardiac inotropy and arrhythmogenesis. Most of the calcium that activates cardiac contraction comes from the sarcoplasmic reticulum (SR) from where it is released through the RyR. The amplitude of the systolic Ca transient depends steeply on the SR Ca content and it is therefore important(More)
BACKGROUND In ventricular myocytes, the majority of structures that couple excitation to the systolic rise of Ca(2+) are located at the transverse tubular (t-tubule) membrane. In the failing ventricle, disorganization of t-tubules disrupts excitation contraction coupling. The t-tubule membrane is virtually absent in the atria of small mammals resulting in(More)
Ageing related stiffening of the vascular system is believed to be in part responsible for a number of clinical outcomes including hypertension and heart failure. In the present study, we sought to determine whether there are alterations in cardiac excitation contraction coupling that may help compensate for the increased vessel stiffness. Experiments were(More)