In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 83, No. 4 ( 2005-04-01), p. 357-366
Abstract:
This study examined whether the effects of FK506-binding protein dissociation from sarcoplasmic reticulum (SR) Ca 2+ release channels on excitation-contraction (EC) coupling changed when SR Ca 2+ reuptake and (or) the trans-sarcolemmal Ca 2+ extrusion were altered. The steady-state twitch Ca 2+ transient (CaT), cell shortening, post-rest caffeine-induced CaT, and Ca 2+ sparks were measured in rat ventricular myocytes using laser-scanning confocal microscopy. In the normal condition, 50 µmol FK506/L significantly increased steady-state CaT, cell shortening, and post-rest caffeine-induced CaT. When the cells were solely perfused with thapsigargin, FK506 did not reduce any of the states, but when low [Ca 2+ ] 0 (0.1 mmol/L) was perfused additionally, FK506 reduced CaT and cell shortening, and accelerated the reduction of post-rest caffeine-induced CaT. FK506 significantly increased Ca 2+ spark frequency in the normal condition, whereas it mainly prolonged duration of individual Ca 2+ sparks under the combination of thapsigargin and low [Ca 2+ ] 0 perfusion. Modification of SR Ca 2+ release by FK506 impaired EC coupling only when released Ca 2+ could not be taken back into the SR and was readily extruded to the extracellular space. Our findings could partly explain the controversy regarding the contribution of FK506-binding protein dissociation to defective EC coupling.Key words: FK506, ryanodine receptor, sarcoplasmic reticulum Ca 2+ -ATPase, Na + /Ca 2+ exchange, excitation-contraction coupling
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2005
detail.hit.zdb_id:
2004356-9
