The review highlights the potential role of the Ca2+-releasing second messenger inositol(1,4,5) tris phosphate [Ins(1,4,5)P3] in initiating arrhythmias and cell death in cardiac pathologies.
Time for primary review 33 days. Cardiac related death occurs rapidly via the development of arrhythmias or more slowly by a progressive decline in mechanical performance reflecting decreased contractile activity as well as loss of viable myocytes. Pathological conditions such as myocardial ischaemia, inflammatory heart diseases and various forms of heart failure are associated with both sudden death and also with a more progressive decrease in cardiac function. Electrophysiological disturbances leading to malignant ventricular arrhythmias are the usual cause of sudden cardiac death, whereas a gradual loss of functional myocytes, or a decline in their performance, underlies heart failure ultimately leading to cardiac decompensation. The mechanisms initiating these scenarios are complex and multifactorial, involving both extracellular and intracellular factors. However, given the continued major contribution of cardiac deaths to overall mortality, understanding the processes which initiate these pathological events is of prime importance. The current review will focus on changes in the intracellular milieu and in particular the potential role of the Ca2+-releasing second messenger inositol(1,4,5) tris phosphate Ins(1,4,5)P3 in initiating arrhythmias and cell death in cardiac pathologies. Ins(1,4,5)P3 is generated along with sn -1,2-diacylglycerol following the activation of either G protein-coupled receptors and phospholipase C-β (PLC-β) isoforms or receptor tyrosine kinases and PLC-γ isoforms 1. The Ins(1,4,5)P3 which is rapidly released into the cytoplasm, especially after activation of G protein-coupled receptors, activates Ins(1,4,5)P3 receptors on Ca2+ stores in the endoplasmic reticulum sarcoplasmic reticulum (SR) in muscle cells causing a rapid and quantal release of Ca2+ 2. In most non-cardiac cell types, this Ins(1,4,5)P3-initiated Ca2+ response can be perpetuated by the process of Ca2+-induced Ca2+ release mediated by either the Ins(1,4,5)P3 receptors or the related family of ryanodine receptors, the overall effect … * Corresponding author. Tel.: +61-3-9522-4387; Fax: +61-3-9521-1362; E-mail: liz.woodcock@baker.edu.au
Elizabeth A. Woodcock (Sun,) conducted a review in Cardiac dysfunction. Ins(1,4,5)P3 was evaluated. The review highlights the potential role of the Ca2+-releasing second messenger inositol(1,4,5) tris phosphate [Ins(1,4,5)P3] in initiating arrhythmias and cell death in cardiac pathologies.