Linearized buffered Ca2+ diffusion in microdomains and its implications for calculation of [Ca2+] at the mouth of a calcium channel.

Immobile and mobile calcium buffers shape the calcium signal close to a channel by reducing and localizing the transient calcium increase to physiological compartments. In this paper, we focus on the impact of mobile buffers in shaping steady-state calcium gradients in the vicinity of an open channel, i.e. within its "calcium microdomain." We present a linear approximation of the combined reaction-diffusion problem, which can be solved explicitly and accounts for an arbitrary number of calcium buffers, either endogenous or added exogenously. It is valid for small saturation levels of the present buffers and shows that within a few hundred nanometers from the channel, standing calcium gradients develop in hundreds of microseconds after channel opening. It is shown that every buffer can be assigned a uniquely defined length-constant as a measure of its capability to buffer calcium close to the channel. The length-constant clarifies intuitively the significance of buffer binding and unbinding kinetics for understanding local calcium signals. Hence, we examine the parameters shaping these steady-state gradients. The model can be used to check the expected influence of single channel calcium microdomains on physiological processes such as excitation-secretion coupling or excitation-contraction coupling and to explore the differential effect of kinetic buffer parameters on the shape of these microdomains.