RYANODINE RECEPTOR ADAPTATION AND CA2-INDUCED CA2+ RELEASE-DEPENDENT CA2+ OSCILLATIONS()

A simplified mechanism that mimics ''adaptation'' of the ryanodine rec eptor (RyR) has been developed and its significance for Ca2+-induced C a2+ release and Ca2+ oscillations investigated. For parameters that re produce experimental data for the RyR from cardiac cells, adaptation o f the RyR in combination with sarco/endoplasmic reticulum Ca2+ ATPase Ca2+ pumps in the internal stores can give rise to either low [Ca-i(2)] steady states or Ca2+ oscillations coexisting with unphysiologicall y high [Ca-i(2+)] steady states. In this closed-cell-type model rapid, adaptation-dependent Ca2+ oscillations occur only in limited ranges o f parameters. In the presence of Ca2+ influx and efflux from outside t he 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 adapta tion 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 ma rked contrast with what is observed for the inositol 1,4,5-trisphospha te receptor for which the biphasic activation and inhibition of its ac tivity by Ca2+ are sufficient to produce oscillations. Results for thi s model are compared with those based on Ca2+-induced Ca2+ release alo ne in the bullfrog sympathetic neuron. This kinetic model should be su itable for analyzing phenomena associated with ''Ca2+ sparks,'' includ ing their merger into Ca2+ waves in cardiac myocytes.