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Inositol 1,4,5‐Trisphosphate And Reperfusion Arrhythmias
Author(s) -
Woodcock Elizabeth A,
Arthur Jane F,
Matkovich Scot J
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03328.x
Subject(s) - phospholipase c , inositol , receptor , stimulation , second messenger system , chemistry , medicine , pharmacology , endocrinology
SUMMARY 1. The present review focuses on the role of the Ca 2+ ‐ releasing second messenger inositol 1,4,5‐trisphosphate (IP 3 ) in initiating arrhythmias during early reperfusion following a period of myocardial ischaemia. 2. Evidence for an arrhythmogenic action of IP 3 was provided by studies showing a correlation between the extent of the increase in IP 3 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 IP 3 could initiate arrhythmias are discussed, with particular emphasis on the role of slow and unscheduled Ca 2+ release. 4. The reperfusion‐induced IP 3 and arrhythmogenic responses can be initiated through either α 1 ‐adrenoceptors or thrombin receptors, but endothelin receptor stimulation was ineffective. Further studies have provided evidence that the noradrenaline‐mediated response was mediated by α 1A ‐receptors, while the α 1B ‐adrenoceptor subtype appeared to be protective. 5. Reperfusion‐induced IP 3 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 Ca 2+ and it seems likely that the rise in Ca 2+ in ischaemia and reperfusion is responsible for the generation of IP 3 , which will, in turn, further exacerbate Ca 2+ overload.