Showing papers by "Michael J. Berridge published in 2006"
TL;DR: Control of cardiac cell contraction and gene transcription provides another example of how the parallel processing of Ca(2+) signalling can occur through microdomains of intracellular Ca( 2+).
507 citations
TL;DR: It is proposed that Ins(1,4,5)P3 receptors support the development of both inotropy and spontaneous pro-arrhythmic Ca2+ signals in ventricular myocytes stimulated with a Gq-coupled agonist.
Abstract: Although ventricular cardiomyocytes express inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptors, it is unclear how these Ca2+ channels contribute to the effects of Gq-coupled agonists. Endothelin-1 augmented the amplitude of pacing-evoked Ca2+ signals (positive inotropy), and caused an increasing frequency of spontaneous diastolic Ca2+-release transients. Both effects of endothelin-1 were blocked by an antagonist of phospholipase C, suggesting that Ins(1,4,5)P3 and/or diacylglycerol production was necessary. The endothelin-1-mediated spontaneous Ca2+ transients were abolished by application of 2-aminoethoxydiphenyl borate (2-APB), an antagonist of Ins(1,4,5)P3 receptors. Incubation of electrically-paced ventricular myocytes with a membrane-permeant Ins(1,4,5)P3 ester provoked the occurrence of spontaneous diastolic Ca2+ transients with the same characteristics and sensitivity to 2-APB as the events stimulated by endothelin-1. In addition to evoking spontaneous Ca2+ transients, stimulation of ventricular myocytes with the Ins(1,4,5)P3 ester caused a positive inotropic effect. The effects of endothelin-1 were compared with two other stimuli, isoproterenol and digoxin, which are known to induce inotropy and spontaneous Ca2+ transients by overloading intracellular Ca2+ stores. The events evoked by isoproterenol and digoxin were dissimilar from those triggered by endothelin-1 in several ways. We propose that Ins(1,4,5)P3 receptors support the development of both inotropy and spontaneous pro-arrhythmic Ca2+ signals in ventricular myocytes stimulated with a Gq-coupled agonist.
122 citations
TL;DR: It is a change in the properties of the Ca2+ transient that seems to carry the information responsible for the remodelling of the cardiac gene transcription programme that leads first to hypertrophy and then to congestive heart failure.
Abstract: In cardiac cells, Ca2+ signals appear as brief transients responsible for controlling both contraction and transcription Information may be encoded in these digital signals through changes in both frequency and shape An increase in Ca2+ signalling contributes to a process of phenotypic remodelling during hypertrophy The increase in Ca2+ that drives the larger contractions may be responsible for switching on a second process of signalosome remodelling to down-regulate the Ca2+ signalling pathway It is a change in the properties of the Ca2+ transient that seems to carry the information responsible for the remodelling of the cardiac gene transcription programme that leads first to hypertrophy and then to congestive heart failure
88 citations