A model for a G-protein-mediated mechanism for synaptic channel modulation

Gabriel Soto, Hans G. Othmer

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)188-213
Number of pages26
JournalMathematical Biosciences
Issue number2
StatePublished - Apr 2006

Bibliographical note

Funding Information:
We like to thank Jon Gottesman for the useful discussions and inputs to this work. This work has been supported by NIH grant 29123 and by the Facultad de Ingenierı́a of Universidad Nacional de la Patagonia San Juan Bosco.


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