Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations.
A simplified mechanism that mimics "adaptation" of the ryanodine receptor (RyR) has been developed and its significance for Ca2+(-)induced Ca2+ release and Ca2+ oscillations investigated. For parameters that reproduce experimental data for the RyR from cardiac cells, adaptation of the RyR in combination with sarco/endoplasmic reticulum Ca2+ ATPase Ca2+ pumps in the internal stores can give rise to either low [Cai2+] steady states or Ca2+ oscillations coexisting with unphysiologically high [Cai2+] steady states. In this closed-cell-type model rapid, adaptation-dependent Ca2+ oscillations occur only in limited ranges of parameters. In the presence of Ca2+ influx and efflux from outside the cell (open-cell model) Ca2+ oscillations occur for a wide range of physiological parameter values and have a period that is determined by the rate of Ca2+ refilling of the stores. Although the rate of adaptation of the RyR has a role in determining the shape and the period of the Ca2+ spike, it is not essential for their existence. This is in marked contrast with what is observed for the inositol 1,4,5-trisphosphate receptor for which the biphasic activation and inhibition of its activity by Ca2+ are sufficient to produce oscillations. Results for this model are compared with those based on Ca2+(-)induced Ca2+ release alone in the bullfrog sympathetic neuron. This kinetic model should be suitable for analyzing phenomena associated with "Ca2+ sparks," including their merger into Ca2+ waves in cardiac myocytes.
Keizer
J
J
Institute of Theoretical Dynamics, University of California, Davis 95616, USA. jekeizer@ucdavis.edu
Levine
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D006321:Heart / Q000502:physiology; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009124:Muscle Proteins / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009991:Oscillometry; D019837:Ryanodine Receptor Calcium Release Channel; D013997:Time Factors
D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium