- Title
- Termination of calcium-induced calcium release by induction decay: an emergent property of stochastic channel gating and molecular scale architecture
- Creator
- Laver, D. R.; Kong, C. H. T.; Imtiaz, M. S.; Cannell, M. B.
- Relation
- NHMRC.631052 http://purl.org/au-research/grants/nhmrc/631052
- Relation
- Journal of Molecular and Cellular Cardiology Vol. 54, p. 98-100
- Publisher Link
- http://dx.doi.org/10.1016/j.yjmcc.2012.10.009
- Publisher
- Academic Press
- Resource Type
- journal article
- Date
- 2013
- Description
- Calcium-induced calcium release (CICR) is an inherently regenerative process due to the Ca2+-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’.
- Subject
- heart; Myocytes; Ca2 + sparks; calcium-induced calcium release; Ryanodine receptors; Excitation–contraction coupling
- Identifier
- http://hdl.handle.net/1959.13/1301289
- Identifier
- uon:20246
- Identifier
- ISSN:0022-2828
- Language
- eng
- Reviewed
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