Sarcoplasmic reticulum calcium release function and FK binding proteins in heart failure: another piece of a complex jigsaw

Abstract

See article by Ono et al. [1] ( pages 323 -331) in thisdefect in FKBP. Aspects investigated include the role of issue.the dissociation of FKBP from RYR on Ca release and the amount of FKBP in SR vesicles isolated from normal and Dysfunction is a complex phenomenon in heart failure.failing hearts. The major finding is that, in heart failure, Most cardiac structures are altered and functional relationthere is a dramatic reduction in FKBP. This corresponds to ships are disrupted. A global picture of the pathophysiolthe observation that application of the immunosuppressant ogy of heart failure is not yet available. However, many agent FK506, to produce dissociation of FKBP12.6 from studies showing modifications of different aspects of RYR in normal hearts, did not cause any further reduction cardiac physiology have been carried out and more pieces in the rate of Ca release from the SR vesicles isolated from of this complex jigsaw are revealed. Amongst these, the failing hearts. This suggests that in heart failure the paper by Ono et al., published in the present issue of regulation of FKBP on RYR is absent, resulting in Cardiovascular Research [1], focuses on the role of FK abnormal and maximal Ca leak. The authors conclude that binding proteins (FKBPs) in heart failure.the modification of the polylysine-induced SR Ca release FKBPs are immunophilin proteins associated with the in heart failure is due to a reduced amount of FKBP. SR Ca release channel (ryanodine receptor (RYR)), whichIn all three studies heart failure was induced by pacing have attracted attention because of their possible inin dogs. The authors have characterized the haemodynamic volvement in the pathophysiology of cardiac muscle. It has aspects of this model and showed a consistent systolic and been suggested that, in muscle, FKBP stabilizes RYR diastolic dysfunction of the failing hearts under invesfunction and this could be involved in the gating of the tigation. Such a model, used previously by other groups RYR [2,3]. Disruption of this binding leads to modi-(e.g [6,7]), represents a well-established technique. Howfications of the channel properties that manifest as appearever, the same authors consider some of the problems in ances of sub-conductance states and / or increased open comparing this model with the chronic failing condition probability (P ) [3]. The paper by Ono et al. [1] is the last observed in human pathophysiology.o of a trilogy from the same research group, which has Considering the evidence from this and other studies, it focused on the importance of the RYR-FKBP relationship may be concluded that in heart failure a reduction in FKBP in heart failure. The first paper [4] showed that, in heart is responsible for a modification of SR Ca release function, failure, polylysine-induced Ca release from SR vesicles therefore causing pathophysiological changes. I would like was decreased, suggesting an impaired gating function of to discuss two points: the role of FKBP in the impairment the RYR. The authors subsequently observed that ...