Microdomain calcium fluctuations as a colored noise process

Abstract

Calcium ions play a key role in subcellular signaling as localized transients of the intracellular calcium concentration modify the activity of ion channels, enzymes and transcription factors, among others. The intracellular calcium concentration is inherently noisy, as diffusion, the transient binding to and dissociation from buffer molecules and stochastically gating calcium channels contribute to the fluctuations of the local copy number of Ca2+ ions. We study the properties of the fluctuating calcium concentration in sub-femtoliter volumes using an exact stochastic simulation algorithm and approximations to the exact stochastic solution. It is shown that the time course of the local calcium concentration represents a colored noise process whose autocorrelation time is a function of buffer kinetics and diffusion constants. Using the chemical Langevin description and the excess buffer approximation of the process, fast approximative algorithms and theoretical connections to the Ornstein-Uhlenbeck process are obtained. In a generic example, we show how calcium noise can couple to the dynamics of a single variable moving in a double-well potential, leading to a colored noise induced transition. Our work shows how a multitude of intracellular signaling pathways may be influenced by the inherent stochasticity of calcium signals, a key messenger in virtually any cell type, and how the calcium signal can be implemented efficiently in cellular signaling models.