Controlling Ca2+-Activated K+ Channels with Models of Ca2+ Buffering in Purkinje Cells

摘要

Intracellular Ca²⁺ concentrations play a crucial role in the physiological interaction between Ca²⁺ channels and Ca²⁺-activated K⁺ channels. The commonly used model, a Ca²⁺ pool with a short relaxation time, fails to simulate interactions occurring at multiple time scales. On the other hand, detailed computational models including various Ca²⁺ buffers and pumps can result in large computational cost due to radial diffusion in large compartments, which may be undesirable when simulating morphologically detailed Purkinje cell models. We present a method using a compensating mechanism to replace radial diffusion and compared the dynamics of different Ca²⁺ buffering models during generation of a dendritic Ca²⁺ spike in a single compartment model of a PC dendritic segment with Ca²⁺ channels of P- and T-type and Ca²⁺-activated K⁺ channels of BK- and SK-type. The Ca²⁺ dynamics models used are (1) a single Ca²⁺ pool; (2) two Ca²⁺ pools, respectively, for the fast and slow transients; (3) detailed Ca²⁺ dynamics with buffers, pump, and diffusion; and (4) detailed Ca²⁺ dynamics with buffers, pump, and diffusion compensation. Our results show that detailed Ca²⁺ dynamics models have significantly better control over Ca²⁺-activated K⁺ channels and lead to physiologically more realistic simulations of Ca²⁺ spikes and bursting. Furthermore, the compensating mechanism largely eliminates the effect of removing diffusion from the model on Ca²⁺ dynamics over multiple time scales.Electronic supplementary materialThe online version of this article (doi:10.1007/s12311-010-0224-3) contains supplementary material, which is available to authorized users.