title: Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cells.
abstract: Intracellular Ca(2+) concentrations play a crucial role in the physiological interaction between Ca(2+) channels and Ca(2+)-activated K(+) channels. The commonly used model, a Ca(2+) pool with a short relaxation time, fails to simulate interactions occurring at multiple time scales. On the other hand, detailed computational models including various Ca(2+) 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 Ca(2+) buffering models during generation of a dendritic Ca(2+) spike in a single compartment model of a PC dendritic segment with Ca(2+) channels of P- and T-type and Ca(2+)-activated K(+) channels of BK- and SK-type. The Ca(2+) dynamics models used are (1) a single Ca(2+) pool; (2) two Ca(2+) pools, respectively, for the fast and slow transients; (3) detailed Ca(2+) dynamics with buffers, pump, and diffusion; and (4) detailed Ca(2+) dynamics with buffers, pump, and diffusion compensation. Our results show that detailed Ca(2+) dynamics models have significantly better control over Ca(2+)-activated K(+) channels and lead to physiologically more realistic simulations of Ca(2+) spikes and bursting. Furthermore, the compensating mechanism largely eliminates the effect of removing diffusion from the model on Ca(2+) dynamics over multiple time scales.
authors.affiliation: Computational Neuroscience Unit, Okinawa Institute of Science and Technology, Okinawa, Japan. anwar@oist.jp
authors.forename: Haroon
authors.initials: H
authors.lastname: Anwar
authors.forename: Sungho
authors.initials: S
authors.lastname: Hong
authors.forename: Erik
authors.initials: E
authors.lastname: De Schutter
mesh_terms: D000465:Algorithms; D002021:Buffers; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020865:Calcium Channels, P-Type / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology; D004058:Diffusion; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D008959:Models, Neurological; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology
chemical_list: D002021:Buffers; D020865:Calcium Channels, P-Type; D020747:Calcium Channels, T-Type; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D002118:Calcium