Inositol 1,4,5-Trisphosphate And Reperfusion Arrhythmias

• Published in: Clinical and Experimental Pharmacology and Physiology 2000-09, Vol.27 (9), p.734-737
• Main Authors: Woodcock, Elizabeth A, Arthur, Jane F, Matkovich, Scot J
• Format: Article
• Language: English
• Subjects: 5- trisphosphate; Animals; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - metabolism; Arrhythmias, Cardiac - physiopathology; arrythmia; Ca2+ overload; Calcium Signaling - physiology; Humans; inositol 1; Inositol 1,4,5-Trisphosphate - physiology; ischaemia; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; reperfusion
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1046/j.1440-1681.2000.03328.x

SUMMARY 1. The present review focuses on the role of the Ca2+‐ releasing second messenger inositol 1,4,5‐trisphosphate (IP3) in initiating arrhythmias during early reperfusion following a period of myocardial ischaemia. 2. Evidence for an arrhythmogenic action of IP3 was provided by studies showing a correlation between the extent of the increase in IP3 and the incidence of arrhythmias in early reperfusion. In addition, phospholipase C inhibitors selective for thrombin receptor stimulation were anti‐arrhythmic only when arrhythmias were thrombin initiated. 3. Mechanisms by which IP3 could initiate arrhythmias are discussed, with particular emphasis on the role of slow and unscheduled Ca2+ release. 4. The reperfusion‐induced IP3 and arrhythmogenic responses can be initiated through either α1‐adrenoceptors or thrombin receptors, but endothelin receptor stimulation was ineffective. Further studies have provided evidence that the noradrenaline‐mediated response was mediated by α1A‐receptors, while the α1B‐adrenoceptor subtype appeared to be protective. 5. Reperfusion‐induced IP3 responses could be inhibited by procedures known to reduce the incidence of arrhythmias under these conditions, including preconditioning, inhibiting Na+/H+ exchange or by dietary supplementation with n‐3 polyunsaturated fatty acids. 6. Inositol 1,4,5‐trisphosphate generation in cardiomyocytes can be facilitated by raising intracellular Ca2+ and it seems likely that the rise in Ca2+ in ischaemia and reperfusion is responsible for the generation of IP3, which will, in turn, further exacerbate Ca2+ overload.