Showing papers by "Istvan Jona published in 2006"

Insights into the regulation of the ryanodine receptor: differential effects of Mg2+ and Ca2+ on ATP binding.

Abstract: Calcium ions are frequently used second messengers in most living organisms. Members of the family of ryanodine sensitive calcium channels (ryanodine receptors, RyRs) are responsible for many important Ca(2+) signaling events in both excitable and nonexcitable cells. The biological activity of these membrane proteins is modulated and regulated by a great variety of different cellular and extracellular effectors, proteins, and small molecules. However, very little is still understood about how the modulators work on a molecular level. The very large size of more than 2 million Da per functional tetrameric RyR unit and its membrane association have made more detailed biochemical and structural analysis extremely challenging.

Cardiomyopathies and sudden cardiac death caused by RyR2 mutations: Are the channels the beginning and the end?

Abstract: See article by Milting et al. [3] (pages 496–505) in this issue. A basic goal of medicine is to cure diseases. Acquired diseases may sometimes be prevented by various methods of exercising, by the “healthy way” of living. Inherited diseases are different; their effective treatment (provided that there is any) requires the recognition of the disease in a sufficiently early stage of life. One – and probably the most promising – way to do so is to establish the link between disorders and genetic alterations. This can be achieved by mapping the mutations corresponding to a given disease, and in the past decade a large number of mutations affecting molecules involved in calcium handling of skeletal and cardiac muscles, including the ryanodine receptor, have been identified [1]. Regarding the cardiac sarcoplasmic reticulum (SR) calcium release channel (RyR2), one of the first published mutations was presented in the pioneering work of Laitinen et al. [2]. In that study, three different RyR2 mutations (P2328S, Q4201R, and V4653F) were associated with familiar polymorphic ventricular tachycardia (FPVT), and each of them was shown to fully co-segregate with the characteristic arrhythmic phenotype. The importance of this kind of knowledge cannot be overestimated, since it makes it possible to recognize a hidden inherited cardiac disorder that exhibits no visible sign of myocardial damage while threatening with close to 30% mortality due to sudden cardiac death (SCD) upon heavy exercise. The article by Milting et al. in this issue of Cardiovascular Research reports two new single nucleotide polymorphisms (G1885E and G1886S) … * Corresponding author. Tel.: +36 52 416634; fax: +36 52 432289. Email address: nanasi{at}phys.dote.hu