https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20204 Sat 24 Mar 2018 08:06:48 AEDT ]]> 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 ]]>