A model for a G-protein-mediated mechanism for synaptic channel modulation.
Neurons communicate with other neurons via specialized structures called synapses, at which the digital voltage signal encoded in an action potential is converted into an analog chemical signal. An action potential that arrives at the presynaptic face triggers release of neurotransmitter from vesicles in a calcium-dependent manner, and the neurotransmitter diffuses across the synaptic cleft and binds to receptors on the post-synaptic face, where it may trigger a postsynaptic action potential. Calcium is a critical component of the release process, and its spatio-temporal dynamics can control the release and can lead to facilitation or augmentation. However, how cells regulate cytoplasmic calcium so that exocytosis can be triggered successfully is still not completely understood. We propose a mechanism, based upon the experimental findings of Barrett and Rittenhouse [C.F. Barrett, A.R. Rittenhouse, Modulation of N-type calcium channel activity by G-proteins and protein kinase C, J. Gen. Physiol. 115 (3) (2000) 277], for the regulation of calcium influx through N-type channels in the presynaptic terminal by PKC and downstream effectors of G-protein activation. This proposed modulatory mechanism consists of a feedback loop involving cytoplasmic calcium, neurotransmitters and G-protein-coupled receptors. We study the dynamics of each component separately and then we address how kinetic properties of the components and the frequency of the stimuli affect the regulatory mechanisms presented here.
Soto
Gabriel
G
School of Mathematics, University of Minnesota, Minneapolis, MN 55455, USA. gabys@math.bu.edu
Othmer
Hans G
HG
D000818:Animals; D002118:Calcium / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D003198:Computer Simulation; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D020864:Calcium Channels, N-Type; D018377:Neurotransmitter Agents; D043562:Receptors, G-Protein-Coupled; D002118:Calcium