7 research outputs found
Spatiotemporal calcium-dynamics in presynaptic terminals
This thesis deals with a newly-developed model for the spatiotemporal calcium dynamics within presynaptic terminals. The model is based on single-protein kinetics and has been used to successfully describe different neuron types such as pyramidal neurons in the rat neocortex and the Calyx of Held of neurons from the rat brainstem. A limited number of parameters had to be adjusted to fluorescence measurements of the calcium concentration. These values can be interpreted as a prediction of the model, and in particular the protein densities can be compared to independent experiments. The contribution of single proteins to the total calcium dynamics has been analysed in detail for voltage-dependent calcium channel, plasma-membrane calcium ATPase, sodium-calcium exchanger, and endogenous as well as exogenous buffer proteins. The model can be used to reconstruct the unperturbed calcium dynamics from measurements using fluorescence indicators. The calcium response to different stimuli has been investigated in view of its relevance for synaptic plasticity. This work provides a first step towards a description of the complete synaptic transmission using single-protein data
A theory of Plasma Membrane Calcium Pump stimulation and activity
The ATP-driven Plasma Membrane Calcium pump or Ca(2+)-ATPase (PMCA) is
characterized by a high affinity to calcium and a low transport rate compared
to other transmembrane calcium transport proteins. It plays a crucial role for
calcium extrusion from cells. Calmodulin is an intracellular calcium buffering
protein which is capable in its Ca(2+) liganded form of stimulating the PMCA by
increasing both the affinity to calcium and the maximum calcium transport rate.
We introduce a new model of this stimulation process and derive analytical
expressions for experimental observables in order to determine the model
parameters on the basis of specific experiments. We furthermore develop a model
for the pumping activity. The pumping description resolves the seeming
contradiction of the Ca(2+):ATP stoichiometry of 1:1 during a translocation
step and the observation that the pump binds two calcium ions at the
intracellular site. The combination of the calcium pumping and the stimulation
model correctly describes PMCA function. We find that the processes of
calmodulin-calcium complex attachment to the pump and of stimulation have to be
separated. Other PMCA properties are discussed in the framework of the model.
The presented model can serve as a tool for calcium dynamics simulations and
provides the possibility to characterize different pump isoforms by different
type-specific parameter sets.Comment: 24 pages, 6 figure
Spatiotemporal calcium-dynamics in presynaptic terminals
This thesis deals with a newly-developed model for the spatiotemporal calcium dynamics within presynaptic terminals. The model is based on single-protein kinetics and has been used to successfully describe different neuron types such as pyramidal neurons in the rat neocortex and the Calyx of Held of neurons from the rat brainstem. A limited number of parameters had to be adjusted to fluorescence measurements of the calcium concentration. These values can be interpreted as a prediction of the model, and in particular the protein densities can be compared to independent experiments. The contribution of single proteins to the total calcium dynamics has been analysed in detail for voltage-dependent calcium channel, plasma-membrane calcium ATPase, sodium-calcium exchanger, and endogenous as well as exogenous buffer proteins. The model can be used to reconstruct the unperturbed calcium dynamics from measurements using fluorescence indicators. The calcium response to different stimuli has been investigated in view of its relevance for synaptic plasticity. This work provides a first step towards a description of the complete synaptic transmission using single-protein data
Spatiotemporal calcium-dynamics in presynaptic terminals
This thesis deals with a newly-developed model for the spatiotemporal calcium dynamics within presynaptic terminals. The model is based on single-protein kinetics and has been used to successfully describe different neuron types such as pyramidal neurons in the rat neocortex and the Calyx of Held of neurons from the rat brainstem. A limited number of parameters had to be adjusted to fluorescence measurements of the calcium concentration. These values can be interpreted as a prediction of the model, and in particular the protein densities can be compared to independent experiments. The contribution of single proteins to the total calcium dynamics has been analysed in detail for voltage-dependent calcium channel, plasma-membrane calcium ATPase, sodium-calcium exchanger, and endogenous as well as exogenous buffer proteins. The model can be used to reconstruct the unperturbed calcium dynamics from measurements using fluorescence indicators. The calcium response to different stimuli has been investigated in view of its relevance for synaptic plasticity. This work provides a first step towards a description of the complete synaptic transmission using single-protein data