https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20246 2+_-dependent gating of ryanodine receptors (RyRs) in the sarco/endoplasmic reticulum (SR) and is critical for cardiac excitation–contraction coupling. This process is seen as Ca²⁺ sparks, which reflect the concerted gating of groups of RyRs in the dyad, a specialised junctional signalling domain between the SR and surface membrane. However, the mechanism(s) responsible for the termination of regenerative CICR during the evolution of Ca²⁺ sparks remain uncertain. Rat cardiac RyR gating was recorded at physiological Ca²⁺, Mg²⁺ and ATP levels and incorporated into a 3D model of the cardiac dyad which reproduced the time-course of Ca²⁺ sparks, Ca²⁺ blinks and Ca²⁺ spark restitution. Model CICR termination was robust, relatively insensitive to the number of dyadic RyRs and automatic. This emergent behaviour arose from the rapid development and dissolution of nanoscopic Ca²⁺ gradients within the dyad. These simulations show that CICR does not require intrinsic inactivation or SR calcium sensing mechanisms for stability and cessation of regeneration that arises from local control at the molecular scale via a process we call ‘induction decay’.]]> Sat 24 Mar 2018 07:59:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27466 2+) into cardiac cells and between their intracellular organelles, and any disruption can lead to arrhythmia and sudden cardiac death. Electrical excitation of the surface membrane activates voltage-dependent L-type Ca²⁺ channels to open and allow Ca²⁺ to enter the cytoplasm. The subsequent increase in cytoplasmic Ca²⁺ concentration activates calcium release channels (RyR2) located at specialised Ca2+ release sites in the sarcoplasmic reticulum (SR), which serves as an intracellular Ca²⁺ store. Animal models have provided valuable insights into how intracellular Ca²⁺ transport mechanisms are altered in human heart failure. The aim of this review is to examine how Ca²⁺ release sites are remodelled in heart failure and how this affects intracellular Ca²⁺ transport with an emphasis on Ca²⁺ release mechanisms in the SR. Current knowledge on how heart failure alters the regulation of RyR2 by Ca²⁺ and Mg²⁺ and how these mechanisms control the activity of RyR2 in the confines of the Ca²⁺ release sites is reviewed.]]> Sat 24 Mar 2018 07:32:43 AEDT ]]>