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1. C-protein is a major component of muscle thick filaments whose function is unknown. We have examined for the first time the role of the regulatory binding domain of C-protein in modulating contraction and intracellular Ca2+ concentration ([Ca2+]i) in intact cardiac myocytes. 2. Rat ventricular myocytes were reversibly permeabilised with the pore-forming(More)
BACKGROUND Many ion channels are preferentially located in caveolae where compartmentalisation/scaffolding with signal transduction components regulates their activity. Channels that are mechanosensitive may be additionally dependent on caveolar control of the mechanical state of the membrane. Here we test which mechanism underlies caveolar-regulation of(More)
BACKGROUND Phospholemman regulates the plasmalemmal sodium pump in excitable tissues. RESULTS In cardiac muscle, a subpopulation of phospholemman with a unique phosphorylation signature associates with other phospholemman molecules but not with the pump. CONCLUSION Phospholemman oligomers exist in cardiac muscle. SIGNIFICANCE Much like phospholamban(More)
In cardiac muscle, the sarcolemmal sodium/potassium ATPase is the principal quantitative means of active transport at the myocyte cell surface, and its activity is essential for maintaining the trans-sarcolemmal sodium gradient that drives ion exchange and transport processes that are critical for cardiac function. The 72-residue phosphoprotein(More)
During vertebrate evolution there has been a shift in the way in which the heart varies cardiac output (the product of heart rate and stroke volume). While mammals, birds, and amphibians increase cardiac output through large increases in heart rate and only modest increases (approximately 30%) in stroke volume, fish and some reptiles use modest increases in(More)
1. Microtubules form part of the cytoskeleton. Their role in adult ventricular myocytes is not well understood although microtubule proliferation has previously been linked with reduced contractile function. 2. We investigated the effect of the anti-tumour drug taxol, a known microtubule polymerizing agent, on Ca2+ handling in adult rat ventricular(More)
Na(V)1.5 sodium channels enhance the invasiveness of breast cancer cells through the acidic-dependent activation of cysteine cathepsins. Here, we showed that the Na(+)/H(+) exchanger type 1 (NHE1) was an important regulator of H(+) efflux in breast cancer cells MDA-MB-231 and that its activity was increased by Na(V)1.5. Na(V)1.5 and NHE1 were colocalized in(More)
The phosphorylation status of the cardiac sarcoplasmic reticular (SR) protein phospholamban determines the activity of the SR Ca(2+)-ATPase. In order to predict SR Ca2+ transport in vivo, it is vital that techniques used to measure the phosphorylation status of phospholamban adequately clamp the endogenous kinases and phosphatases which modify(More)
Concentration-dependent changes in cyclic AMP (cAMP), site-specific phosphorylation of phospholamban, the intracellular calcium ([Ca2+]i) transient and contraction were measured in isolated rat ventricular myocytes exposed to the beta-adrenoceptor agonist isoprenaline. Cyclic AMP was measured by [125I]-cAMP scintillation proximity assay, phosphorylation of(More)
This review focuses on the complex interactions between two major regulators of cardiac function; Ca2+ and stretch. Initial consideration is given to the effect of stretch on myocardial contractility and details the rapid and slow increases in contractility. These are shown to be related to two diverse changes in Ca2+ handling (enhanced myofilament Ca2+(More)