Showing papers by "David A. Eisner published in 2005"

Stability and instability of regulation of intracellular calcium.

Abstract: [Ca2+]i is used as a signal in many tissues. In this review we discuss the mechanisms that regulate [Ca2+]i and, importantly, what determines their stability. Brief mention is made of the effects of feedback gain and delays on stability. The control of cytoplasmic Ca concentration is shown to be generally stable as Ca pumping is essentially an instantaneous function of [Ca2+]i. In contrast, regulation of the Ca content of intracellular stores may be less stable. One example of this is instability in the control of sarcoplasmic reticulum (SR) Ca content in cardiac muscle. An increase of SR Ca content increases the systolic Ca transient amplitude. This in turn decreases Ca influx into the cell and increases efflux, thereby restoring SR Ca to control levels. This feedback system has an inherent delay and is potentially unstable if the gain is increased beyond a certain level. This instability produces Ca transients of alternating amplitude and may contribute to the clinical syndrome of pulsus alternans.

Something old, something new: changing views on the cellular mechanisms of heart failure.

Abstract: See article by Fauconnier et al. [84] (pages 204–212) in this issue. Despite improvements in therapy, mortality in heart failure (HF) remains high, and there is a need for alternative and additional approaches [1,2]. The possibility of replacement and/or supporting the failing heart with new cardiomyocytes from stem cells, implanted or recruited locally, is one of the exciting possibilities under investigation [3]. Other approaches aim at improving the function of the failing myocytes. Although the temporal and causal relationship between the development of chronic HF and myocyte dysfunction remains unclear [4], there is little doubt that at the time of advanced HF, the isolated myocytes have reduced contractility, in particular under normal physiological stress, i.e. at physiological heart rates and in the response to adrenergic stimulation. The first trials with chronic inotropic therapy, however, had a very poor outcome, and the idea was abandoned for quite a long time [5]. However, new ideas to improve contractility of the myocytes are growing from recent insights into the cellular mechanisms underlying the contractile dysfunction and the link to signals for remodeling. In this editorial, we will briefly review the background of excitation–contraction coupling and changes in heart failure against which these views developed and discuss some future perspectives. The process of excitation–contraction coupling has been reviewed extensively and is schematically illustrated in Fig. 1 [6,7]. Central in the link between membrane depolarization and contraction is the transient elevation of [Ca2+]i, or [Ca2+]i transient. Fig. 1 Schematic of excitation–contraction coupling. During the action potential, Ca2+ enters the cell through voltage-activated Ca2+ channels, with a small additional amount entering through the Na/Ca exchanger, NCX, depending on the [Na+]i. This Ca2+ acts as trigger to activate the Ca … *Corresponding author. Tel.: +32 16 347153; fax: +32 16 345844. Email address: Karin.Sipido{at}med.kuleuven.be