https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 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 ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33272 2+ release channels in the sarcoplasmic reticulum in striated muscle which play an important role in excitation-contraction coupling and cardiac pacemaking. Single channel recordings have revealed a wealth of information about ligand regulation of RyRs from mammalian skeletal and cardiac muscle (RyR1 and RyR2, respectively). RyR subunit has a Ca²⁺ activation site located in the luminal and cytoplasmic domains of the RyR. These sites synergistically feed into a common gating mechanism for channel activation by luminal and cytoplasmic Ca²⁺. RyRs also possess two inhibitory sites in their cytoplasmic domains with Ca²⁺ affinities of the order of 1 µM and 1 mM. Magnesium competes with Ca²⁺ at these sites to inhibit RyRs and this plays an important role in modulating their Ca²⁺-dependent activity in muscle. This review focuses on how these sites lead to RyR modulation by Ca²⁺ and Mg²⁺ and how these mechanisms control Ca²⁺ release in excitation-contraction coupling and cardiac pacemaking.]]> Mon 24 Sep 2018 13:26:20 AEST ]]>