Integrated luminal and cytosolic aspects of the calcium release control.

We propose here a unitary approach to the luminal and cytosolic control of calcium release. A minimal number of model elements that realistically describe different data sets are combined and adapted to correctly respond to various physiological constraints. We couple the kinetic properties of the inositol 1,4,5 trisphosphate receptor/calcium channel with the dynamics of Ca(2+) and K(+) in both the lumen and cytosol, and by using a detailed simulation approach, we propose that local (on a radial distance approximately 2 micro m) calcium oscillations in permeabilized cells are driven by the slow inactivation of channels organized in discrete clusters composed of between six and 15 channels. Moreover, the character of these oscillations is found to be extremely sensitive to K(+), so that the cytosolic and luminal calcium variations are in or out of phase if the store at equilibrium has tens or hundreds micro M Ca(2+), respectively, depending on the K(+) gradient across the reticulum membrane. Different patterns of calcium signals can be reproduced through variation of only a few parameters.